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Mititelu A, Grama A, Colceriu MC, Benţa G, Popoviciu MS, Pop TL. Role of Interleukin 6 in Acute Pancreatitis: A Possible Marker for Disease Prognosis. Int J Mol Sci 2024; 25:8283. [PMID: 39125854 PMCID: PMC11311934 DOI: 10.3390/ijms25158283] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2024] [Revised: 07/24/2024] [Accepted: 07/27/2024] [Indexed: 08/12/2024] Open
Abstract
Acute pancreatitis (AP) is a significant cause of morbidity, even in children, and is frequently associated with systemic manifestations. There are many cytokines involved in the inflammatory response characteristic of this disease. Interleukin 6 (IL-6) is one of the most important cytokines involved in AP, beginning from cellular injury and continuing to the systemic inflammatory response and distant organ involvement. IL-6 is a multifunctional cytokine that regulates acute-phase response and inflammation. It is produced by various cells and exerts its biological role on many cells through its high-affinity complex receptor. IL-6 has been investigated as a predicting maker for severe forms of AP. Many studies have validated the use of IL-6 serum levels in the first 48 h as a reliable marker for severe evolution and multisystemic involvement. Still, it has not been used in daily practice until now. This review discusses the main binding mechanisms by which IL-6 triggers cellular response and the AP pathogenetic mechanisms in which IL-6 is involved. We then emphasize the promising role of IL-6 as a prognostic marker, which could be added as a routine marker at admission in children with AP.
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Affiliation(s)
- Alexandra Mititelu
- 2nd Pediatric Discipline, Department of Mother and Child, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania; (A.M.); (M.-C.C.); (G.B.); (T.L.P.)
| | - Alina Grama
- 2nd Pediatric Discipline, Department of Mother and Child, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania; (A.M.); (M.-C.C.); (G.B.); (T.L.P.)
- 2nd Pediatric Clinic, Emergency Clinical Hospital for Children, 400177 Cluj-Napoca, Romania
| | - Marius-Cosmin Colceriu
- 2nd Pediatric Discipline, Department of Mother and Child, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania; (A.M.); (M.-C.C.); (G.B.); (T.L.P.)
| | - Gabriel Benţa
- 2nd Pediatric Discipline, Department of Mother and Child, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania; (A.M.); (M.-C.C.); (G.B.); (T.L.P.)
| | | | - Tudor Lucian Pop
- 2nd Pediatric Discipline, Department of Mother and Child, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania; (A.M.); (M.-C.C.); (G.B.); (T.L.P.)
- 2nd Pediatric Clinic, Emergency Clinical Hospital for Children, 400177 Cluj-Napoca, Romania
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Yang DJ, Chen KL, Lv ZY, Zhou B, Zhou ZG, Li Y. PD-L1 blockade in mitigating severe acute pancreatitis induced pancreatic damage through modulation of immune cell apoptosis. Int Immunopharmacol 2024; 133:112081. [PMID: 38652963 DOI: 10.1016/j.intimp.2024.112081] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2024] [Revised: 04/07/2024] [Accepted: 04/10/2024] [Indexed: 04/25/2024]
Abstract
Acute pancreatitis (AP) is a prevalent gastrointestinal disorder. The immune response plays a crucial role in AP progression. However, the impact of immune regulatory checkpoint PD-L1 on severe acute pancreatitis (SAP) remains uncertain. Hence, this study aimed to examine the influence of PD-L1 on SAP. We assessed PD-L1 expression in neutrophils and monocytes obtained from SAP patients. We induced SAP in C57BL/6J mice, PD-L1 gene-deficient mice, and PD-L1 humanized mice using intraperitoneal injections of cerulein plus lipopolysaccharide. Prior to the initial cerulein injection, a PD-L1 inhibitor was administered. Pancreatic tissues were collected for morphological and immunohistochemical evaluation, and serum levels of amylase, lipase, and cytokines were measured. Flow cytometry analysis was performed using peripheral blood cells. The expression of PD-L1 in neutrophils and monocytes was significantly higher in SAP patients compared to healthy individuals. Likewise, the expression of PD-L1 in inflammatory cells in the peripheral blood of SAP-induced C57BL/6J mice was notably higher than in the control group. In mice with PD-L1 deficiency, SAP model exhibited lower pancreatic pathology scores, amylase, lipase, and cytokine levels compared to wild-type mice. PD-L1 deletion resulted in reduced neutrophil apoptosis, leading to an earlier peak in neutrophil apoptosis. Furthermore, it decreased early monocyte apoptosis and diminished the peak of T lymphocyte apoptosis. Within the SAP model, administration of a PD-L1 inhibitor reduced pancreatic pathology scores, amylase, lipase, and cytokine levels in both C57BL/6J mice and PD-L1 humanized mice. These findings suggest that inhibiting PD-L1 expression can alleviate the severity of SAP.
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Affiliation(s)
- Du-Jiang Yang
- Institute of Digestive Surgery, West China Hospital, Sichuan University, No. 1 Ke-yuan-si-lu, Chengdu 610093, Sichuan Province, China; Division of Pancreatic Surgery, Department of General Surgery, West China Hospital, Sichuan University, No. 37, Guoxue Alley, Chengdu 610041, Sichuan Province, China
| | - Ke-Ling Chen
- Institute of Digestive Surgery, West China Hospital, Sichuan University, No. 1 Ke-yuan-si-lu, Chengdu 610093, Sichuan Province, China
| | - Zhao-Ying Lv
- Institute of Digestive Surgery, West China Hospital, Sichuan University, No. 1 Ke-yuan-si-lu, Chengdu 610093, Sichuan Province, China
| | - Bin Zhou
- Institute of Digestive Surgery, West China Hospital, Sichuan University, No. 1 Ke-yuan-si-lu, Chengdu 610093, Sichuan Province, China
| | - Zong-Guang Zhou
- Institute of Digestive Surgery, West China Hospital, Sichuan University, No. 1 Ke-yuan-si-lu, Chengdu 610093, Sichuan Province, China
| | - Yuan Li
- Institute of Digestive Surgery, West China Hospital, Sichuan University, No. 1 Ke-yuan-si-lu, Chengdu 610093, Sichuan Province, China.
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Poulsen VV, Hadi A, Werge MP, Karstensen JG, Novovic S. Circulating Biomarkers Involved in the Development of and Progression to Chronic Pancreatitis-A Literature Review. Biomolecules 2024; 14:239. [PMID: 38397476 PMCID: PMC10887223 DOI: 10.3390/biom14020239] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2023] [Revised: 02/13/2024] [Accepted: 02/16/2024] [Indexed: 02/25/2024] Open
Abstract
Chronic pancreatitis (CP) is the end-stage of continuous inflammation and fibrosis in the pancreas evolving from acute- to recurrent acute-, early, and, finally, end-stage CP. Currently, prevention is the only way to reduce disease burden. In this setting, early detection is of great importance. Due to the anatomy and risks associated with direct sampling from pancreatic tissue, most of our information on the human pancreas arises from circulating biomarkers thought to be involved in pancreatic pathophysiology or injury. The present review provides the status of circulating biomarkers involved in the development of and progression to CP.
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Affiliation(s)
- Valborg Vang Poulsen
- Pancreatitis Center East, Gastrounit, Copenhagen University Hospital—Amager and Hvidovre, 2000 Copenhagen, Denmark; (V.V.P.); (A.H.); (M.P.W.); (J.G.K.)
| | - Amer Hadi
- Pancreatitis Center East, Gastrounit, Copenhagen University Hospital—Amager and Hvidovre, 2000 Copenhagen, Denmark; (V.V.P.); (A.H.); (M.P.W.); (J.G.K.)
| | - Mikkel Parsberg Werge
- Pancreatitis Center East, Gastrounit, Copenhagen University Hospital—Amager and Hvidovre, 2000 Copenhagen, Denmark; (V.V.P.); (A.H.); (M.P.W.); (J.G.K.)
| | - John Gásdal Karstensen
- Pancreatitis Center East, Gastrounit, Copenhagen University Hospital—Amager and Hvidovre, 2000 Copenhagen, Denmark; (V.V.P.); (A.H.); (M.P.W.); (J.G.K.)
- Department of Clinical Medicine, University of Copenhagen, 2000 Copenhagen, Denmark
| | - Srdan Novovic
- Pancreatitis Center East, Gastrounit, Copenhagen University Hospital—Amager and Hvidovre, 2000 Copenhagen, Denmark; (V.V.P.); (A.H.); (M.P.W.); (J.G.K.)
- Department of Clinical Medicine, University of Copenhagen, 2000 Copenhagen, Denmark
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Oikonomou P, Nikolaou C, Papachristou F, Sovatzidis A, Lambropoulou M, Giouleka C, Kontaxis V, Linardoutsos D, Papalois A, Pitiakoudis M, Tsaroucha A. Eugenol Reduced ΜPO, CD45 and HMGB1 Expression and Attenuated the Expression of Leukocyte Infiltration Markers in the Intestinal Tissue in Biliopancreatic Duct Ligation-Induced Pancreatitis in Rats. MEDICINA (KAUNAS, LITHUANIA) 2023; 60:74. [PMID: 38256335 PMCID: PMC10820626 DOI: 10.3390/medicina60010074] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/26/2023] [Revised: 11/30/2023] [Accepted: 12/26/2023] [Indexed: 01/24/2024]
Abstract
Background and Objectives: Inflammation and dysregulation in the intestinal barrier function in acute pancreatitis (AP) trigger pancreatic lesions, systemic inflammatory response, and multiple organ dysfunction. Eugenol, as the main component of clove (Syzygium aromaticum), is known for its antioxidant and anti-inflammatory properties. We studied the potentially beneficial effect of eugenol in a rodent model of biliopancreatic duct ligation-induced AP. Materials and Methods: Rats were randomly divided into three groups: Sham, AP, and AP + eugenol (15 mg/kg/day). Serum TNFα, IL-6, IL-18, and resistin levels, as well as IL-6, TNFα, MPO, HMGB1, and CD45 tissue expression, were determined at various timepoints after the induction of AP. Results: Eugenol attenuated hyperemia and inflammatory cell infiltration in the intestinal mucosal, submucosal, and muscular layers. IL-6 and resistin serum levels were significantly reduced in the AP + eugenol group, while serum TNFα and IL-18 levels remained unaffected overall. TNFα pancreatic and intestinal expression was attenuated by eugenol at 72 h, while IL-6 expression was affected only in the pancreas. MPO, CD45, and HMGB1 intestinal expression was significantly reduced in eugenol-treated rats. Conclusions: Eugenol managed to attenuate the inflammatory response in the intestine in duct ligation-induced AP in rats.
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Affiliation(s)
- Panagoula Oikonomou
- Postgraduate Program in Hepatobiliary and Pancreatic Surgery, 2nd Department of Surgery, Faculty of Medicine, Democritus University of Thrace, 68100 Alexandroupolis, Greece; (A.S.); (C.G.); (V.K.); (D.L.); (M.P.); (A.T.)
- Laboratory of Experimental Surgery and Surgical Research, Faculty of Medicine, Democritus University of Thrace, 68100 Alexandroupolis, Greece; (C.N.); (F.P.)
| | - Christina Nikolaou
- Laboratory of Experimental Surgery and Surgical Research, Faculty of Medicine, Democritus University of Thrace, 68100 Alexandroupolis, Greece; (C.N.); (F.P.)
| | - Fotini Papachristou
- Laboratory of Experimental Surgery and Surgical Research, Faculty of Medicine, Democritus University of Thrace, 68100 Alexandroupolis, Greece; (C.N.); (F.P.)
| | - Apostolos Sovatzidis
- Postgraduate Program in Hepatobiliary and Pancreatic Surgery, 2nd Department of Surgery, Faculty of Medicine, Democritus University of Thrace, 68100 Alexandroupolis, Greece; (A.S.); (C.G.); (V.K.); (D.L.); (M.P.); (A.T.)
| | - Maria Lambropoulou
- Laboratory of Histology-Embryology, Faculty of Medicine, Democritus University of Thrace, 68100 Alexandroupolis, Greece;
| | - Charikleia Giouleka
- Postgraduate Program in Hepatobiliary and Pancreatic Surgery, 2nd Department of Surgery, Faculty of Medicine, Democritus University of Thrace, 68100 Alexandroupolis, Greece; (A.S.); (C.G.); (V.K.); (D.L.); (M.P.); (A.T.)
| | - Vasileios Kontaxis
- Postgraduate Program in Hepatobiliary and Pancreatic Surgery, 2nd Department of Surgery, Faculty of Medicine, Democritus University of Thrace, 68100 Alexandroupolis, Greece; (A.S.); (C.G.); (V.K.); (D.L.); (M.P.); (A.T.)
| | - Dimitrios Linardoutsos
- Postgraduate Program in Hepatobiliary and Pancreatic Surgery, 2nd Department of Surgery, Faculty of Medicine, Democritus University of Thrace, 68100 Alexandroupolis, Greece; (A.S.); (C.G.); (V.K.); (D.L.); (M.P.); (A.T.)
| | - Apostolos Papalois
- Experimental Research Center, ELPEN Pharmaceuticals, Pikermi, 19009 Athens, Greece;
| | - Michael Pitiakoudis
- Postgraduate Program in Hepatobiliary and Pancreatic Surgery, 2nd Department of Surgery, Faculty of Medicine, Democritus University of Thrace, 68100 Alexandroupolis, Greece; (A.S.); (C.G.); (V.K.); (D.L.); (M.P.); (A.T.)
| | - Alexandra Tsaroucha
- Postgraduate Program in Hepatobiliary and Pancreatic Surgery, 2nd Department of Surgery, Faculty of Medicine, Democritus University of Thrace, 68100 Alexandroupolis, Greece; (A.S.); (C.G.); (V.K.); (D.L.); (M.P.); (A.T.)
- Laboratory of Experimental Surgery and Surgical Research, Faculty of Medicine, Democritus University of Thrace, 68100 Alexandroupolis, Greece; (C.N.); (F.P.)
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Venkatesh K, Glenn H, Delaney A, Andersen CR, Sasson SC. Fire in the belly: A scoping review of the immunopathological mechanisms of acute pancreatitis. Front Immunol 2023; 13:1077414. [PMID: 36713404 PMCID: PMC9874226 DOI: 10.3389/fimmu.2022.1077414] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2022] [Accepted: 12/21/2022] [Indexed: 01/13/2023] Open
Abstract
Introduction Acute pancreatitis (AP) is characterised by an inflammatory response that in its most severe form can cause a systemic dysregulated immune response and progression to acute multi-organ dysfunction. The pathobiology of the disease is unclear and as a result no targeted, disease-modifying therapies exist. We performed a scoping review of data pertaining to the human immunology of AP to summarise the current field and to identify future research opportunities. Methods A scoping review of all clinical studies of AP immunology was performed across multiple databases. Studies were included if they were human studies of AP with an immunological outcome or intervention. Results 205 studies met the inclusion criteria for the review. Severe AP is characterised by significant immune dysregulation compared to the milder form of the disease. Broadly, this immune dysfunction was categorised into: innate immune responses (including profound release of damage-associated molecular patterns and heightened activity of pattern recognition receptors), cytokine profile dysregulation (particularly IL-1, 6, 10 and TNF-α), lymphocyte abnormalities, paradoxical immunosuppression (including HLA-DR suppression and increased co-inhibitory molecule expression), and failure of the intestinal barrier function. Studies including interventions were also included. Several limitations in the existing literature have been identified; consolidation and consistency across studies is required if progress is to be made in our understanding of this disease. Conclusions AP, particularly the more severe spectrum of the disease, is characterised by a multifaceted immune response that drives tissue injury and contributes to the associated morbidity and mortality. Significant work is required to develop our understanding of the immunopathology of this disease if disease-modifying therapies are to be established.
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Affiliation(s)
- Karthik Venkatesh
- Malcolm Fisher Department of Intensive Care, Royal North Shore Hospital, St Leonards, NSW, Australia
- The Kirby Institute, The University of New South Wales, Kensington, NSW, Australia
| | - Hannah Glenn
- Malcolm Fisher Department of Intensive Care, Royal North Shore Hospital, St Leonards, NSW, Australia
| | - Anthony Delaney
- Malcolm Fisher Department of Intensive Care, Royal North Shore Hospital, St Leonards, NSW, Australia
- Division of Critical Care, The George Institute for Global Health, Newtown, NSW, Australia
| | - Christopher R. Andersen
- Malcolm Fisher Department of Intensive Care, Royal North Shore Hospital, St Leonards, NSW, Australia
- The Kirby Institute, The University of New South Wales, Kensington, NSW, Australia
- Division of Critical Care, The George Institute for Global Health, Newtown, NSW, Australia
| | - Sarah C. Sasson
- The Kirby Institute, The University of New South Wales, Kensington, NSW, Australia
- Institute of Clinical Pathology and Medical Research, Westmead Hospital, Westmead, NSW, Australia
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Mazilescu LI, Parmentier C, Kalimuthu SN, Ganesh S, Kawamura M, Goto T, Noguchi Y, Selzner M, Reichman TW. Normothermic ex situ pancreas perfusion for the preservation of porcine pancreas grafts. Am J Transplant 2022; 22:1339-1349. [PMID: 35258859 PMCID: PMC9314088 DOI: 10.1111/ajt.17019] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Revised: 01/28/2022] [Accepted: 02/23/2022] [Indexed: 01/25/2023]
Abstract
Pancreas transplantation improves and extends the life of patients with insulin-dependent diabetes. Pancreata from extended criteria donors have been increasingly used due to the scarcity of available grafts. Normothermic ex situ pancreas perfusion (NESPP) can keep grafts metabolically active, potentially allowing for assessment and organ repair, and could improve outcomes of marginal grafts. A novel NESPP technique was developed and tested. Porcine pancreata were removed after a short period of warm ischemia and subjected to 6 h of NESPP. Perfusion parameters, potential graft assessment markers and graft injury were measured. Next, pancreata subjected to 3 h of NESPP were transplanted and animals were followed for up to 3 days. Graft function and injury post-transplantation were evaluated. Using this novel system of perfusion, pancreata were perfused for an extended period of time with minimal edema. Histology at the end of perfusion showed intact islet cells with only mild signs of tissue injury. NESPP transplanted grafts showed immediate function after transplantation, with glucose levels in normal range. NESPP maintains a physiologic environment and excellent graft function without causing significant graft injury. Porcine pancreas transplantation is feasible and allows for in vivo graft assessment of pancreas function and injury after NESPP.
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Affiliation(s)
- Laura I. Mazilescu
- Ajmera Transplant ProgramToronto General HospitalTorontoOntarioCanada,Division of NephrologyThe Hospital for Sick ChildrenTorontoOntarioCanada,Department of General, Visceral, and Transplantation SurgeryUniversity Hospital EssenEssenGermany,Division of General SurgeryToronto General HospitalUniversity Health NetworkTorontoOntarioCanada
| | | | - Sangeetha N. Kalimuthu
- Department of PathologyUniversity Health Network and University of TorontoTorontoOntarioCanada
| | - Sujani Ganesh
- Ajmera Transplant ProgramToronto General HospitalTorontoOntarioCanada
| | - Masataka Kawamura
- Ajmera Transplant ProgramToronto General HospitalTorontoOntarioCanada
| | - Toru Goto
- Ajmera Transplant ProgramToronto General HospitalTorontoOntarioCanada
| | - Yuki Noguchi
- Ajmera Transplant ProgramToronto General HospitalTorontoOntarioCanada
| | - Markus Selzner
- Ajmera Transplant ProgramToronto General HospitalTorontoOntarioCanada,Division of General SurgeryToronto General HospitalUniversity Health NetworkTorontoOntarioCanada
| | - Trevor W. Reichman
- Ajmera Transplant ProgramToronto General HospitalTorontoOntarioCanada,Division of General SurgeryToronto General HospitalUniversity Health NetworkTorontoOntarioCanada
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IL-10-1082G>A polymorphism, use of opioids and age affect the course of acute pancreatitis. Eur J Gastroenterol Hepatol 2021; 32:178-185. [PMID: 32804849 DOI: 10.1097/meg.0000000000001875] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
PURPOSE We aimed to determine the association of two of the most important functional polymorphisms of IL-8 and IL-10 with the clinical course and outcome of acute pancreatitis. METHOD Ninety-three patients with acute pancreatitis were genotyped for IL-8-251T>A and IL-10-1082G>A using PCR-RFLP. The severity of the disease was determined based on the Atlanta Classification system. RESULTS In patients treated with opioids, the odds for severe form of acute pancreatitis, its complications, and death were increased. Advanced age was associated with higher odds of organ/multiple organ failure and other systemic complications. Multivariate logistic regression analyses confirmed the observed effect of age and use of opioids, and revealed higher odds for the development of severe form of acute pancreatitis [P = 0.017, odds ratio (OR): 4.324, 95% confidence interval (CI): 1.305-14.323], its complications in general (P = 0.011, OR: 4.936, 95% CI: 1.442-16.897), pancreatic necrosis (P = 0.032, OR: 3.922, 95% CI: 1.122-13.707) and systemic inflammatory response syndrome (P = 0.037, OR: 3.838, 95% CI: 1.085-13.583) in the absence of IL-10-1082G>A variant allele. The effect of IL-8 -251T>A on acute pancreatitis severity or mortality was not detected. CONCLUSION Our study suggests the IL-10 -1082A allele as a protective factor in acute pancreatitis. Opioid analgesics treatment in acute pancreatitis is associated with severity, complications and mortality, while advanced age increases the risk of systemic complications.
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Chhatriya B, Sarkar P, Nath D, Ray S, Das K, Mohapatra SK, Goswami S. Pilot study identifying circulating miRNA signature specific to alcoholic chronic pancreatitis and its implication on alcohol-mediated pancreatic tissue injury. JGH OPEN 2020; 4:1079-1087. [PMID: 33319040 PMCID: PMC7731805 DOI: 10.1002/jgh3.12389] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/02/2020] [Revised: 06/15/2020] [Accepted: 06/28/2020] [Indexed: 11/12/2022]
Abstract
Background and Aim Alcohol exerts its effects on organs in multiple ways. Alcoholic chronic pancreatitis (ACP) is a disease in which alcohol triggers the pathological changes in pancreas, leading to chronic inflammation and fibrosis. The molecular mechanism behind these changes is not clear. Identification of key circulating miRNA changes in ACP patients and determination of the fraction that is secreted from diseased pancreas not only could serve as potential biomarker for assessing disease severity, but also could help identifying the molecular alterations prevailing in the organ precipitating the disease, to some extent. Methods We performed microRNA microarray using the Affymetrix miRNA 4.0 platform to identify differentially expressed miRNAs in serum of ACP patients as compared to alcoholic control individuals and then found out how many of them could be pancreas-specific and exosomally secreted. We further analyzed a pancreatitis-specific gene expression data set to find out the differentially expressed genes in diseased pancreas and explored the possible role of those selected miRNAs in regulation of gene expression in ACP. Results We identified 14 miRNAs differentially expressed in both serum and pancreas and also identified their experimentally validated targets. Transcription factors modulating the miRNA expression in an alcohol-dependent manner were also identified and characterized to derive the miRNA-gene-TF interaction network responsible for progression of the disease. Conclusions Differentially expressed miRNA signature demonstrated significant changes in both pro- and anti-inflammatory pathways probably balancing the chronic inflammation in the pancreas. Our findings also suggested possible involvement of pancreatic stellate cells in disease progression.
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Affiliation(s)
| | - Piyali Sarkar
- Department of Cytogenetics Tata Medical Centre Kolkata India
| | - Debashis Nath
- Department of Medicine Indira Gandhi Memorial Hospital Agartala India
| | - Sukanta Ray
- School of Digestive and Liver Diseases Institute of Post Graduate Medical Education and Research Kolkata India
| | - Kshaunish Das
- School of Digestive and Liver Diseases Institute of Post Graduate Medical Education and Research Kolkata India
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Early laboratory biomarkers for severity in acute pancreatitis; A systematic review and meta-analysis. Pancreatology 2020; 20:1302-1311. [PMID: 32938552 DOI: 10.1016/j.pan.2020.09.007] [Citation(s) in RCA: 43] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2020] [Revised: 08/25/2020] [Accepted: 09/05/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND/OBJECTIVES Acute pancreatitis is complicated by local and systemic complications in 20-30% of the patients. Accurate prediction of severity may be important for clinical decision making. Our aim is to identify and compare the accuracy of laboratory biomarkers that predict severity and complications in adult patients. METHODS Medline, EMBASE, Web of Science and Cochrane Library (1993 to August 2020) were searched for studies with an unselected population of patients with acute pancreatitis, that contains accuracy data for ≥1 laboratory biomarker(s) and/or APACHE-II score for the prediction of a patient outcomes of interest during the first 48 h of admission. The primary outcome is moderate severe or severe acute pancreatitis (MSAP/SAP). Secondary outcomes are severe acute pancreatitis, pancreatic necrosis and organ failure. Risk of bias was assed using QUADAS-2. Biomarkers extracted from ≥3 unique sources, were analyzed using hierarchical summary receiver operating characteristic (HSROC) and bivariate model analysis. RESULTS In total, 181 studies were included in the qualitative analysis reporting on 29 biomarkers. For the primary outcome at admission, summary sensitivities and specificities were, respectively, 87% (95% CI 69-95%) and 88% (95% CI 80-93%) for IL-6 at a threshold of >50 pg/ml, 72% (95% CI 64-79%) and 76% (95% CI 67-84%) for an APACHE-II score of ≥8, and 53% (95% CI 35-71%) and 82% (95% CI 74-88%) for CRP >150 mg/l. HSROC curve analysis confirmed these results. CONCLUSION This study indicates superiority of IL-6 for the early prediction of MSAP/SAP and may be used for to guide clinical decision making.
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Shin JY, Choi JW, Kim DG, Zhou ZQ, Shin YK, Seo JH, Song HJ, Choi BM, Bae GS, Park SJ. Protective effects of Coenzyme Q10 against acute pancreatitis. Int Immunopharmacol 2020; 88:106900. [PMID: 32829089 DOI: 10.1016/j.intimp.2020.106900] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2020] [Revised: 08/05/2020] [Accepted: 08/12/2020] [Indexed: 02/07/2023]
Abstract
Acute pancreatitis (AP) refers to inflammation in the pancreas, which may lead to death in severe cases. Coenzyme Q10 (Q10), generally known to generate energy, plays an important role as an anti-oxidant and anti-inflammatory effector. Here, we showed the effect of Q10 on inflammatory response in murine AP model. For this study, we induced AP by injection of cerulein intraperitoneally or pancreatic duct ligation (PDL) in mice. The level of cytokines and digestive enzymes were measured in pancreas, and blood. All pancreatic tissues were excised for investigation such as histological changes, infiltration of immune cells. Administration of Q10 attenuated the severity of AP and its associated pulmonary complication as shown by reduction of acinar cell death, parenchymal edema, inflammatory cell infiltration and alveolar thickening in both cerulein-induced AP and PDL-induced AP. Moreover, reduction of the cytokines such as interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α were observed in pancreas and pancreatic acinar cells by Q10. Furthermore, Q10 reduced the infiltration of immune cells such as monocytes and neutrophils and augmentation of chemokines such as CC chemokine-2 (CCL2) and C-X-C chemokine-2 (CXCL2) in pancreas of AP mice. In addition, Q10 deactivates the phosphorylation of extracellular signal-regulated kinase (ERK) and c-jun NH2-terminal kinase (JNK) in pancreas. In conclusion, these observations suggest that Q10 could attenuate the pancreatic damage and its associated pulmonary complications via inhibition of inflammatory cytokines and inflammatory cell infiltration and that the deactivation of ERK and JNK by Q10 might contribute to the attenuation of AP.
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Affiliation(s)
- Joon Yeon Shin
- Department of Herbology, School of Korean Medicine, Wonkwang University, Iksan-daero 460, Iksan, Jeollabuk-do 54538, Republic of Korea
| | - Ji-Won Choi
- Department of Herbology, School of Korean Medicine, Wonkwang University, Iksan-daero 460, Iksan, Jeollabuk-do 54538, Republic of Korea; Hanbang Cardio-Renal Syndrome Research Center, Wonkwang University, Iksan-daero 460, Iksan, Jeollabuk-do 54538, Republic of Korea
| | - Dong-Gu Kim
- Hanbang Cardio-Renal Syndrome Research Center, Wonkwang University, Iksan-daero 460, Iksan, Jeollabuk-do 54538, Republic of Korea
| | - Zi Qi Zhou
- Department of Herbology, School of Korean Medicine, Wonkwang University, Iksan-daero 460, Iksan, Jeollabuk-do 54538, Republic of Korea
| | - Yong Kook Shin
- Department of Bio Pharmaceutical Industry, Semyung University, Semyeong-ro 65, Jecheon, Chungcheongbuk-do 27136, Republic of Korea
| | - Jae Ho Seo
- Department of Biochemistry, School of Medicine, Wonkwang University, Iksan-daero 460, Iksan, Jeollabuk-do 54538, Republic of Korea
| | - Ho-Joon Song
- Department of Herbology, School of Korean Medicine, Wonkwang University, Iksan-daero 460, Iksan, Jeollabuk-do 54538, Republic of Korea
| | - Byung-Min Choi
- Department of Biochemistry, School of Medicine, Wonkwang University, Iksan-daero 460, Iksan, Jeollabuk-do 54538, Republic of Korea.
| | - Gi-Sang Bae
- Hanbang Cardio-Renal Syndrome Research Center, Wonkwang University, Iksan-daero 460, Iksan, Jeollabuk-do 54538, Republic of Korea; Department of Pharmacology, School of Korean Medicine, Wonkwang University, Iksan-daero 460, Iksan, Jeollabuk-do 54538, Republic of Korea; Research Center of Traditional Korean Medicine, Wonkwang University, Iksan-daero 460, Iksan, Jeollabuk-do 54538, Republic of Korea.
| | - Sung-Joo Park
- Department of Herbology, School of Korean Medicine, Wonkwang University, Iksan-daero 460, Iksan, Jeollabuk-do 54538, Republic of Korea; Hanbang Cardio-Renal Syndrome Research Center, Wonkwang University, Iksan-daero 460, Iksan, Jeollabuk-do 54538, Republic of Korea.
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11
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Mohr S, Amylidi-Mohr SK, Stadelmann P, Sculean A, Persson R, Eick S, Surbek DV. Systemic Inflammation in Pregnant Women With Periodontitis and Preterm Prelabor Rupture of Membranes: A Prospective Case-Control Study. Front Immunol 2019; 10:2624. [PMID: 31787985 PMCID: PMC6854050 DOI: 10.3389/fimmu.2019.02624] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2019] [Accepted: 10/22/2019] [Indexed: 12/22/2022] Open
Abstract
Aims: Periodontal disease is associated with adverse pregnancy outcome, but the underlying pathophysiologic mechanism is still unknown. In this prospective, longitudinal, non-interventional case-control study, 45 women with preterm premature rupture of membranes and 26 controls with uncomplicated pregnancies were examined at three time-points (T1: 20–34 weeks of gestations; T2: within 48 h after delivery; T3: 4–6 weeks post partum). Examinations included subgingival, blood, vaginal, and placenta sampling for microbiologic, cytokine, and histology assessment. Objective of this study was to test the hypothesis that systemic inflammatory changes and not specific bacteria are predominantly involved in the association between periodontal disease and adverse pregnancy outcome. Results: Demographic data and gestational age at T1 were comparable between groups. While there was no correlation between vaginal and gingival fluid microbiome, cytokine levels in the assessed compartments differed between cases, and controls. Vaginal smears did not show a higher rate of abnormal flora in the cases at the onset of preterm premature rupture of membranes. Number and variety of bacteria in the case group placental membranes and vagina were higher, but these bacteria were not found in membranes at birth. Conclusions: On the basis of our results we speculate that an inflammatory pathway sequentially involving periodontal tissue, maternal serum, and finally vaginal compartment contributes to the underlying pathomechanism involved in preterm premature rupture of membranes associated with periodontitis.
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Affiliation(s)
- Stefan Mohr
- Department of Obstetrics and Gynecology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Sofia K Amylidi-Mohr
- Department of Obstetrics and Gynecology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Pascale Stadelmann
- Department of Periodontology, School of Dental Medicine, University of Bern, Bern, Switzerland
| | - Anton Sculean
- Department of Periodontology, School of Dental Medicine, University of Bern, Bern, Switzerland
| | - Rutger Persson
- Department of Periodontology, School of Dental Medicine, University of Bern, Bern, Switzerland.,Oral Health Sciences, Division of Health Sciences, Research Professor, University of Washington, Seattle, WA, United States
| | - Sigrun Eick
- Department of Periodontology, School of Dental Medicine, University of Bern, Bern, Switzerland
| | - Daniel V Surbek
- Department of Obstetrics and Gynecology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
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Pesonen E, Passov A, Andersson S, Suojaranta R, Niemi T, Raivio P, Salmenperä M, Schramko A. Glycocalyx Degradation and Inflammation in Cardiac Surgery. J Cardiothorac Vasc Anesth 2019; 33:341-345. [DOI: 10.1053/j.jvca.2018.04.007] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2018] [Indexed: 12/22/2022]
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Gene polymorphisms in the interleukins gene and the risk of acute pancreatitis: A meta-analysis. Cytokine 2019; 115:50-59. [PMID: 30634098 DOI: 10.1016/j.cyto.2018.12.003] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2018] [Revised: 10/25/2018] [Accepted: 12/10/2018] [Indexed: 02/08/2023]
Abstract
Single nucleotide polymorphisms (SNPs) within the interleukins (IL) gene may affect the risk of acute pancreatitis. Many epidemiological studies have reported an association between the IL gene and acute pancreatitis risk, but the results remain inconsistent. Given the controversial available data, we carried out a meta-analysis to systematically evaluate and clarify the association between IL gene polymorphisms and AP. A systematic search of studies for this association was obtained from the PubMed, EMBASE, Web of Science and Chinese National Knowledge Infrastructure (CNKI) databases until June 1, 2017. We also searched the references of the included studies to identify additional studies. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were used to pool the effect size. Stata12.0 was used for whole statistical analysis. Fifteen studies that contained 3371 AP cases and 3506 controls were included in final combination. Overall, a significant association was found between the IL-8-251 T/A (rs4073) polymorphism, the IL-10-1082 A/G (rs1800896) polymorphism and the AP risk in four genetic models (homozygote model, recessive model, dominant model, allele model). Meanwhile, individuals with IL-1β+3954 C/T (rs1143634, (homozygote model, recessive model)), IL-1β -511 C/T (rs16944, (dominant model)) and IL-6-634C/G (rs1800796, (allele model)) polymorphism were associated with an increased risk of AP. No evidence of an association was found between IL and 10-592 C/A (rs1800872) and IL-10-819 C/T (rs1800871) polymorphism and AP risk.
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14
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Arriaga-Pizano L, Boscó-Gárate I, Martínez-Ordaz JL, Wong-Baeza I, Gutiérrez-Mendoza M, Sánchez-Fernandez P, López-Macías C, Isibasi A, Pelaez-Luna M, Cérbulo-Vázquez A, Torres-González R, Ferat-Osorio E. High Serum Levels of High-Mobility Group Box 1 (HMGB1) and Low Levels of Heat Shock Protein 70 (Hsp70) are Associated with Poor Prognosis in Patients with Acute Pancreatitis. Arch Med Res 2018; 49:504-511. [PMID: 30947809 DOI: 10.1016/j.arcmed.2019.02.003] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2018] [Revised: 02/03/2019] [Accepted: 02/18/2019] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Cell damage in Acute Pancreatitis (AP) lead to release of cytokines and HMGB1 and Hsp70. While Hsp70 plays a role in cytoprotection, when released to extracellular milieu constitutes, as HMGB1, a danger signal and trigger pro-inflammatory responses. These molecules seem to be related to the clinical progression; but because no evidence exists about them as molecular network in AP development, we quantify HSP70, HMGB1, and cytokines in patients with AP and search for correlations with severity and prognosis. METHODS Fifteen patients with AP were included. The average age was 52 years. Six patients had mild pancreatitis, 4 were moderately severe and 5 with a severe form. Blood samples were taken within the first 24 h, at 3d and 7d from the start. Serum HMGB1 and Hsp70 were determined using ELISA; TNF-α, IL-1β, IL-6, IL-8, IL-10 and IL-12p70 were determined by bead based immuassay. RESULTS Of all 15 patients recruited, 4 were women. Eight patients had APACHEII score higher than 8. Two patients died from AP related complications. Increase in serum HMGB1 and decrease of Hsp70 were associated with the severity and mortality. TNF-α, IL-6 and IL-8 were higher in patients that did not survive, in those with an APACHE II >8, and in those with severe AP. CONCLUSIONS High HMGB1 and low Hsp70 were associated with poor prognosis. Hsp70 might play a protective role in AP. TNF-α, IL-6, IL-8, HMGB1 and Hsp70 during hospital admissions might serve to evaluate risk of death due to AP.
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Affiliation(s)
- Lourdes Arriaga-Pizano
- Unidad de Investigación Médica en Inmunoquímica, Unidad Médica de Alta Especialidad, Hospital de Especialidades, Dr. Bernardo Sepúlveda Gutiérrez, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de México, México
| | - Ilka Boscó-Gárate
- Unidad de Investigación Médica en Inmunoquímica, Unidad Médica de Alta Especialidad, Hospital de Especialidades, Dr. Bernardo Sepúlveda Gutiérrez, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de México, México
| | - José Luis Martínez-Ordaz
- Servicio de Cirugía Gastrointestinal, Unidad Médica de Alta Especialidad, Hospital de Especialidades Dr. Bernardo Sepúlveda Gutiérrez, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de México, México
| | - Isabel Wong-Baeza
- Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Ciudad de México, México
| | - Mireille Gutiérrez-Mendoza
- Unidad de Investigación Médica en Inmunoquímica, Unidad Médica de Alta Especialidad, Hospital de Especialidades, Dr. Bernardo Sepúlveda Gutiérrez, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de México, México
| | - Patricio Sánchez-Fernandez
- Servicio de Cirugía Gastrointestinal, Unidad Médica de Alta Especialidad, Hospital de Especialidades Dr. Bernardo Sepúlveda Gutiérrez, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de México, México
| | - Constantino López-Macías
- Unidad de Investigación Médica en Inmunoquímica, Unidad Médica de Alta Especialidad, Hospital de Especialidades, Dr. Bernardo Sepúlveda Gutiérrez, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de México, México
| | - Armando Isibasi
- Unidad de Investigación Médica en Inmunoquímica, Unidad Médica de Alta Especialidad, Hospital de Especialidades, Dr. Bernardo Sepúlveda Gutiérrez, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de México, México
| | - Mario Pelaez-Luna
- Laboratorio de Hígado, Páncreas y Motilidad Intestinal, Departamento de Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México, Cuidad de México, México
| | - Arturo Cérbulo-Vázquez
- Programa de Estudios Combinados en Medicina, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de México, México
| | - Rubén Torres-González
- Dirección de Educación e Investigación en Salud, Hospital de Traumatología y Ortopedia, Dr. Victorio de la Fuente Narváez, Instituto Mexicano del Seguro Social, Ciudad de México, México
| | - Eduardo Ferat-Osorio
- Unidad de Investigación Médica en Inmunoquímica, Unidad Médica de Alta Especialidad, Hospital de Especialidades, Dr. Bernardo Sepúlveda Gutiérrez, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de México, México; Servicio de Cirugía Gastrointestinal, Unidad Médica de Alta Especialidad, Hospital de Especialidades Dr. Bernardo Sepúlveda Gutiérrez, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de México, México.
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15
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Abstract
BACKGROUND The association between interleukin-10 (IL-10) gene rs1800896 polymorphism and susceptibility to acute pancreatitis (AP) has been investigated in several studies, but with contradictory findings. Therefore, a comprehensive meta-analysis is needed to assess the strength of such association. METHODS Literatures on PubMed, EMBASE, and CNKI were searched to identify relevant studies. The strength of association between IL-10 gene rs1800896 polymorphism and AP risk was assessed using pooled odds ratios and 95% confidence intervals. RESULTS Totally 7 case-control studies involving 1527 cases and 1511 controls were identified. Analyses proved that IL-10 gene rs1800896 polymorphism was significantly associated with an increased risk of AP. Stratification analysis of ethnicity found such significant association only among Asians, but not Caucasians. CONCLUSION IL-10 gene rs1800896 polymorphism increases the risk of AP.
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Affiliation(s)
| | - Ailing Liu
- Department of Emergency, Yi Du Central Hospital of Wei Fang, Shandong
| | - Bingzhi Zhou
- Department of Emergency, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | | | - Guangjun Jin
- Department of Emergency, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
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16
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Wang Y, Fuentes HE, Attar BM, Jaiswal P, Demetria M. Evaluation of the prognostic value of neutrophil to lymphocyte ratio in patients with hypertriglyceridemia-induced acute pancreatitis. Pancreatology 2017; 17:893-897. [PMID: 29030078 DOI: 10.1016/j.pan.2017.10.001] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2017] [Revised: 09/23/2017] [Accepted: 10/03/2017] [Indexed: 02/08/2023]
Abstract
INTRODUCTION Recent studies attribute promising prognostic values to various inflammatory biomarkers in acute pancreatitis, including the following: the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and red cell distribution width (RDW). We aimed to determine the performance of these biomarkers for detecting disease severity in patients with hypertriglyceridemia-induced acute pancreatitis (HTG-AP). METHODS We retrospectively reviewed 110 patients with HTG-AP and compared the NLR, PLR, and RDW in different severity groups. We performed receiver-operating characteristic (ROC) analysis to identify the optimal cut-off value for NLR to predict severe AP. RESULTS NLR was significantly higher in patients with severe AP than mild and moderately severe AP (14.6 vs. 6.9, p < 0.001), and higher with organ failure upon presentation (9.1 vs. 7.1, p = 0.026). After dichotomization by the optimal cut-off value of 10 as determined by the ROC curve, the high-NLR group had a significantly longer length of stay (9.1 vs. 6.6 days, p = 0.001), duration of nil per os (4.9 vs. 3.7 days, p = 0.007), and higher rates of complications, including systemic inflammatory response syndrome (81.5% vs. 44.6%, p = 0.001) and persistent acute kidney injury (25.9% vs. 3.6%, p < 0.001). High NLR independently predicted severe acute pancreatitis in multivariate analysis (Odds ratio 6.71, p = 0.019). CONCLUSION NLR represents an inexpensive, readily available test with a promising value to predict disease severity in HTG-AP. Among the three inflammatory biomarkers, NLR has the highest discriminatory capacity for severe HTG-AP, with an optimal cut-off value of 10.
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Affiliation(s)
- Yuchen Wang
- Department of Internal Medicine, John H Stroger Hospital of Cook County, Chicago, IL, United States.
| | - Harry E Fuentes
- Department of Internal Medicine, John H Stroger Hospital of Cook County, Chicago, IL, United States
| | - Bashar M Attar
- Department of Gastroenterology, Rush University Medical Center, Chicago, IL, United States; Division of Gastroenterology and Hepatology, John H Stroger Hospital of Cook County, Chicago, IL, United States
| | - Palash Jaiswal
- Department of Internal Medicine, John H Stroger Hospital of Cook County, Chicago, IL, United States
| | - Melchor Demetria
- Division of Gastroenterology and Hepatology, John H Stroger Hospital of Cook County, Chicago, IL, United States
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17
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Li N, Wang B, Cai S, Liu P. The Role of Serum High Mobility Group Box 1 and Interleukin‐6 Levels in Acute Pancreatitis: A Meta‐Analysis. J Cell Biochem 2017; 119:616-624. [PMID: 28618057 DOI: 10.1002/jcb.26222] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2017] [Accepted: 06/14/2017] [Indexed: 12/14/2022]
Affiliation(s)
- Nuo Li
- Department of GastroenterologyThe Fourth Affiliated Hospital of China Medical UniversityShenyang110032P.R. China
| | - Bao‐Ming Wang
- Department of InterventionThe Fourth Affiliated Hospital of China Medical UniversityShenyang110032P.R. China
| | - Shuang Cai
- Department of GastroenterologyThe Fourth Affiliated Hospital of China Medical UniversityShenyang110032P.R. China
| | - Peng‐Liang Liu
- Department of GastroenterologyThe Fourth Affiliated Hospital of China Medical UniversityShenyang110032P.R. China
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18
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Yoo K, Suh KY, Choi GH, Kwak IS, Seo DK, Kym D, Yoon H, Cho YS, Kim HO. Serial Changes of Heat Shock Protein 70 and Interleukin-8 in Burn Blister Fluid. Ann Dermatol 2017; 29:194-199. [PMID: 28392647 PMCID: PMC5383745 DOI: 10.5021/ad.2017.29.2.194] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2016] [Revised: 07/22/2016] [Accepted: 07/27/2016] [Indexed: 12/22/2022] Open
Abstract
Background It has been reported that heat shock protein 70 (HSP70) and interleukin-8 (IL-8) play an important role in cells during the wound healing process. However, there has been no report on the effect of HSP70 and IL-8 on the blisters of burn patients. Objective This study aimed to evaluate the serial quantitative changes of HSP70 and IL-8 in burn blisters. Methods Twenty-five burn patients were included, for a total of 36 cases: twenty cases on the first day, six cases on the second, five cases on the third, three cases on the fourth, and two cases on the fifth. A correlation analysis was performed to determine the relationship between the concentration of HSP70 and IL-8 and the length of the treatment period. Results The HSP70 concentration was the highest on the first day, after which it decreased down to near zero. Most HSP70 was generated during the first 12 hours after the burn accident. There was no correlation between the concentration of HSP70 on the first day and the length of the treatment period. No measurable concentration of IL-8 was detected before 5 hours, but the concentration started to increase after 11 hours. The peak value was measured on the fourth day. Conclusion While HSP70 increased in the first few hours and decreased afterwards, IL-8 was produced after 11 hours and increased afterward in burn blister fluid. These findings provide new evidence on serial changes of inflammatory mediators in burn blister fluid.
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Affiliation(s)
- Kicheol Yoo
- Department of Emergency Medicine, Hangang Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea
| | - Kang Yeol Suh
- Department of Emergency Medicine, Hangang Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea
| | - Gi Hun Choi
- Department of Emergency Medicine, Hangang Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea
| | - In-Suk Kwak
- Department of Anesthesiology and Pain Medicine, Hangang Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea
| | - Dong Kook Seo
- Department of Plasticsurgery, Hangang Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea
| | - Dohern Kym
- Department of Surgery, Hangang Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea
| | - Hyeon Yoon
- Burn Institute, Hangang Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea
| | - Yong Se Cho
- Department of Dermatology, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea
| | - Hye One Kim
- Department of Dermatology, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea
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Immunopathogenesis of pancreatitis. Mucosal Immunol 2017; 10:283-298. [PMID: 27848953 DOI: 10.1038/mi.2016.101] [Citation(s) in RCA: 141] [Impact Index Per Article: 17.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2016] [Accepted: 10/06/2016] [Indexed: 02/04/2023]
Abstract
The conventional view of the pathogenesis of acute and chronic pancreatitis is that it is due to a genetic- or environment-based abnormality of intracellular acinar trypsinogen activation and thus to the induction of acinar cell injury that, in turn, sets in motion an intra-pancreatic inflammatory process. More recent studies, reviewed here, present strong evidence that while such trypsinogen activation is likely a necessary first step in the inflammatory cascade underlying pancreatitis, sustained pancreatic inflammation is dependent on damage-associated molecular patterns-mediated cytokine activation causing the translocation of commensal (gut) organisms into the circulation and their induction of innate immune responses in acinar cells. Quite unexpectedly, these recent studies reveal that the innate responses involve activation of responses by an innate factor, nucleotide-binding oligomerization domain 1 (NOD1), and that such NOD1 responses have a critical role in the activation/production of nuclear factor-kappa B and type I interferon. In addition, they reveal that chronic inflammation and its accompanying fibrosis are dependent on the generation of IL-33 by injured acinar cells and its downstream induction of T cells producing IL-13. These recent studies thus establish that pancreatitis is quite a unique form of inflammation and one susceptible to newer, more innovative therapy.
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20
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Manohar M, Verma AK, Venkateshaiah SU, Sanders NL, Mishra A. Chronic Pancreatitis Associated Acute Respiratory Failure. MOJ IMMUNOLOGY 2017; 5:00149. [PMID: 29399623 PMCID: PMC5793936 DOI: 10.15406/moji.2017.05.00149] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Pancreatitis is a condition characterized by parenchymal inflammation of the pancreas, which is often associated with lung injury due to low level of oxygen and the condition is termed as acute pancreatitis-associated lung injury (APALI). Clinical reports indicated that ~ 20% to 50% of patients from low oxygen levels in blood with acute respiratory distress syndrome (ARDS). ARDS is a severe form of acute lung injury (ALI), a pulmonary disease with impaired airflow making patients difficult to breathe. ALI is frequently observed in patients with severe acute pancreatitis. Approximately one third of severe pancreatitis patients develop acute lung injury and acute respiratory distress syndrome that account for 60% of all deaths within the first week. The major causes of ALI and ARDS are sepsis, trauma, aspiration, multiple blood transfusion, and most importantly acute pancreatitis. The molecular mechanisms of ALI and ARDS are still not well explored, but available reports indicate the involvement of several pro-inflammatory mediators including cytokines (TNF-α, IL-1β, IL-6) and chemokines [like interleukin-8 (IL-8) and macrophage inhibitory factor (MIF)], as well as macrophage polarization regulating the migration and pulmonary infiltration of neutrophils into the pulmonary interstitial tissue, causing injury to the pulmonary parenchyma. Acute lung injury and acute respiratory distress syndrome in acute pancreatitis remains an unsolved issue and needs more research and resources to develop effective treatments and therapies. However, recent efforts have tested several molecules in an experimental model and showed promising results as a treatment option. The current review summarized the mechanism that is operational in pancreatitis-associated acute respiratory failure and respiratory distress syndrome in patients and current treatment options.
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Affiliation(s)
- Murli Manohar
- Department of Medicine and Section of Pulmonary Diseases, Tulane Eosinophilic Disorder Center, Tulane University School of Medicine, USA
| | - Alok K Verma
- Department of Medicine and Section of Pulmonary Diseases, Tulane Eosinophilic Disorder Center, Tulane University School of Medicine, USA
| | - Sathisha Upparahalli Venkateshaiah
- Department of Medicine and Section of Pulmonary Diseases, Tulane Eosinophilic Disorder Center, Tulane University School of Medicine, USA
| | | | - Anil Mishra
- Department of Medicine and Section of Pulmonary Diseases, Tulane Eosinophilic Disorder Center, Tulane University School of Medicine, USA
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Gillies N, Pendharkar SA, Asrani VM, Mathew J, Windsor JA, Petrov MS. Interleukin-6 is associated with chronic hyperglycemia and insulin resistance in patients after acute pancreatitis. Pancreatology 2016; 16:748-55. [PMID: 27401909 DOI: 10.1016/j.pan.2016.06.661] [Citation(s) in RCA: 59] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2016] [Revised: 06/17/2016] [Accepted: 06/29/2016] [Indexed: 12/11/2022]
Abstract
BACKGROUND Diabetes is a pervasive disease, with a mounting prevalence and burden on health care systems. Under this collective term of diabetes falls diabetes after diseases of the exocrine pancreas, a condition which was previously under-recognised and often mislabeled as type 2 diabetes mellitus and is now increasingly acknowledged as a stand-alone entity. However, there is a paucity of clinical studies investigating the underlying pathophysiology of diabetes after acute pancreatitis, the most frequent disease of the pancreas. This study aimed to investigate the role of adipocytokines in glucose metabolism after acute pancreatitis. METHODS This was a cross-sectional follow-up study of a patient cohort diagnosed with acute pancreatitis. Fasting venous blood samples were collected to analyse markers of glucose metabolism (fasting blood glucose, haemoglobin A1c, homeostasis model assessment (HOMA-IR) as a measure of insulin resistance) and adypocytokines (adiponectin, interleukin-6, leptin, monocyte chemoattractant protein-1, retinol binding protein-4, resistin, and tumor necrosis factor-α). Participants were categorized into two groups: normoglycemia after acute pancreatitis and chronic hyperglycemia after acute pancreatitis (CHAP). Binary logistic regression and linear regression analyses were used to investigate the association between each of the adipocytokines and markers of glucose metabolism. Potential confounders were adjusted for in multivariate analyses. RESULTS A total of 83 patients with acute pancreatitis were included, of whom 19 developed CHAP. Interleukin-6 was significantly associated with CHAP in both unadjusted and adjusted models (p = 0.030 and p = 0.018, respectively). Further, it was also significantly associated with HOMA-IR in both unadjusted and adjusted models (p = 0.029 and p = 0.037, respectively). Other adipocytokines were not significantly associated with markers of glucose metabolism. CONCLUSION Interleukin-6 appears to be implicated in the development of chronic hyperglycemia and insulin resistance in patients after acute pancreatitis. It may become a potential target in the prevention and early treatment of diabetes after diseases of the exocrine pancreas.
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Affiliation(s)
- Nicola Gillies
- Department of Surgery, University of Auckland, New Zealand
| | | | | | - Juby Mathew
- Department of Surgery, University of Auckland, New Zealand
| | - John A Windsor
- Department of Surgery, University of Auckland, New Zealand
| | - Maxim S Petrov
- Department of Surgery, University of Auckland, New Zealand.
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Shamoon M, Deng Y, Chen YQ, Bhatia M, Sun J. Therapeutic implications of innate immune system in acute pancreatitis. Expert Opin Ther Targets 2015; 20:73-87. [PMID: 26565751 DOI: 10.1517/14728222.2015.1077227] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
INTRODUCTION Acute pancreatitis (AP) is an inflammatory disorder of the pancreas encompassing a cascade of cellular and molecular events. It starts from premature activation of zymogens with the involvement of innate immune system to a potential systemic inflammatory response and multiple organ failure. Leukocytes are the major cell population that participate in the propagation of the disease. Current understanding of the course of AP is still far from complete, limiting treatment options mostly to conservative supportive care. Emerging evidence has pointed to modulation of the immune system for strategic therapeutic development, by mitigating the inflammatory response and severity of AP. In the current review, we have focused on the role of innate immunity in the condition and highlighted therapeutics targeting it for treatment of this challenging disease. AREAS COVERED The current review has aimed to elaborate in-depth understanding of specific roles of innate immune cells, derived mediators and inflammatory pathways that are involved in AP. Summarizing the recent therapeutics and approaches applied experimentally that target immune responses to attenuate AP. EXPERT OPINION The current state of knowledge on AP, limitations of presently available therapeutic approaches and the promise of therapeutic implications of innate immune system in AP are discussed.
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Affiliation(s)
- Muhammad Shamoon
- a 1 Jiangnan University, School of Food Science and Technology, The Synergetic Innovation Center of Food Safety and Nutrition, State Key Laboratory of Food Science and Technology , Wuxi, Jiangsu, China
| | - Yuanyuan Deng
- a 1 Jiangnan University, School of Food Science and Technology, The Synergetic Innovation Center of Food Safety and Nutrition, State Key Laboratory of Food Science and Technology , Wuxi, Jiangsu, China
| | - Yong Q Chen
- a 1 Jiangnan University, School of Food Science and Technology, The Synergetic Innovation Center of Food Safety and Nutrition, State Key Laboratory of Food Science and Technology , Wuxi, Jiangsu, China
| | - Madhav Bhatia
- b 2 University of Otago, Inflammation Research Group, Department of Pathology , Christchurch, 2 Riccarton Avenue, P.O. Box 4345, Christchurch 8140, New Zealand
| | - Jia Sun
- a 1 Jiangnan University, School of Food Science and Technology, The Synergetic Innovation Center of Food Safety and Nutrition, State Key Laboratory of Food Science and Technology , Wuxi, Jiangsu, China
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Staubli SM, Oertli D, Nebiker CA. Laboratory markers predicting severity of acute pancreatitis. Crit Rev Clin Lab Sci 2015; 52:273-83. [PMID: 26173077 DOI: 10.3109/10408363.2015.1051659] [Citation(s) in RCA: 156] [Impact Index Per Article: 15.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Acute pancreatitis (AP) is an inflammatory disease of highly variable severity, ranging from mild cases with low mortality to severe cases with high mortality. Numerous biomarkers have been studied as potential early predictors of the severity of this disease so that treatment can be optimally tailored to prevent complications. We aim to present and discuss the most relevant biomarkers for early severity assessment in AP that have been studied to date. We review the current literature on biomarkers that have been used to predict the severity in AP. C-reactive protein (CRP) is still considered to be the gold standard, with a cut-off value of 150 mg/ml 48 h after disease onset. Other markers, including procalcitonin (PCT) and interleukin 6 (IL-6) have been implemented in some hospitals, but are not used on a routine basis. Most other markers, including acute phase proteins (LBP, SAA, PTX3), cytokines (Il-8, TNF-a, MIF), activation peptides of pancreatic proteases (TAP, CAPAP, PLAP), antiproteases (AAT, a2M), adhesion molecules (ICAM-1, selectins, E-cadherin) and leukocyte-derived enzymes (PA2, PMN-E) have shown some promising results but have not been routinely implemented. Furthermore, new and interesting biomarkers (Copeptin, TRX-1, Ang-2, E-2) have shown good results, but more research is needed to determine if they could play a role in the future. Various reasons why new markers for disease severity have not been adopted in daily routine include low accuracy, cumbersome laboratory techniques and high cost. Despite these difficulties, research is still very active in finding new markers to predict the severity of AP.
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Affiliation(s)
| | - Daniel Oertli
- a Department of General Surgery , University Hospital Basel , Basel , Switzerland
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Immune Mechanisms of Pancreatitis. Mucosal Immunol 2015. [DOI: 10.1016/b978-0-12-415847-4.00088-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
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Akinosoglou K, Gogos C. Immune-modulating therapy in acute pancreatitis: Fact or fiction. World J Gastroenterol 2014; 20:15200-15215. [PMID: 25386069 PMCID: PMC4223254 DOI: 10.3748/wjg.v20.i41.15200] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2014] [Revised: 05/21/2014] [Accepted: 06/17/2014] [Indexed: 02/06/2023] Open
Abstract
Acute pancreatitis (AP) is one of the most common diseases of the gastrointestinal tract, bearing significant morbidity and mortality worldwide. Current treatment of AP remains unspecific and supportive and is mainly targeted to aggressively prevent systemic complications and organ failure by intensive care. As acute pancreatitis shares an indistinguishable profile of inflammation with sepsis, therapeutic approaches have turned towards modulating the systemic inflammatory response. Targets, among others, have included pro- and anti-inflammatory modulators, cytokines, chemokines, immune cells, adhesive molecules and platelets. Even though, initial results in experimental models have been encouraging, clinical implementation of immune-regulating therapies in acute pancreatitis has had a slow progress. Main reasons include difficulty in clinical translation of experimental data, poor understanding of inflammatory response time-course, flaws in experimental designs, need for multimodal approaches and commercial drawbacks. Whether immune-modulation in acute pancreatitis remains a fact or just fiction remains to be seen in the future.
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The antioxidant profiles, lysosomal and membrane enzymes activity in patients with acute pancreatitis. Mediators Inflamm 2014; 2014:376518. [PMID: 25298618 PMCID: PMC4178910 DOI: 10.1155/2014/376518] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2014] [Revised: 08/19/2014] [Accepted: 08/19/2014] [Indexed: 12/20/2022] Open
Abstract
Oxidative stress and inflammatory mediators, such as IL-6, play an important role in the pathophysiology of acute pancreatitis. The study was aimed to assess the degree of the pro/antioxidative imbalance and estimate which antioxidant plays a role in the maintenance of pro/antioxidative balance during acute pancreatitis. The study was investigated in the blood of 32 patients with acute pancreatitis and 37 healthy subjects. IL-6 concentration as early marker of inflammation was determinated. The intensity of oxidative stress was assessed by TBARS concentration. To investigate antioxidative status, the GPx and Cu/Zn SOD activities and the levels of GSH, MT, SH groups, and TRAP were measured. The concentrations of Cu and Zn as ions participating in the maintenance of antioxidant enzymes stability and playing a role in the course of disease were determinated. The activities of GGT, AAP, NAG, and β-GD as markers of tissue damage were also measured. An increase in IL-6 concentration, which correlated with Ranson criteria, and an increase in GPx activity, levels of MT, TBARS, or GGT, and NAG activities in patients group compared to healthy subjects were demonstrated. A decrease in GSH level in patients group compared to control group was noted. The studies suggest that GPx/GSH and MT play the role of the first line of defence against oxidative stress and pro/antioxidant imbalance in the course of acute pancreatitis.
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Vlachos S, Tsaroucha AK, Konstantoudakis G, Papachristou F, Trypsianis G, Schizas D, Vaos G, Simopoulos C. Serum profiles of M30, M65 and interleukin-17 compared with C-reactive protein in patients with mild and severe acute pancreatitis. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2014; 21:911-8. [PMID: 25214429 DOI: 10.1002/jhbp.162] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND Several studies state that a test of severity early in the course of acute pancreatitis is still needed. In this prospective study, an assay of the biomarkers M30 and M65 as well as of interleukin 17 (IL-17) is investigated. METHODS One hundred and fifty patients and 70 controls were evaluated. The prognostic value of M30, M65 and their ratio M30/M65 is assessed by ELISA. The same method is used for the study of IL-17. RESULTS At 24 h after symptom onset, the concentrations of M30 and M65 as well as their ratio, differed significantly in severe compared to mild disease (P = 0.016). C-reactive protein (CRP) was significantly higher (P < 0.001) in severe pancreatitis on the same day. The sensitivity of M65 to show severe acute pancreatitis at 24 h was 100% for values above the cut-off point of 428.15 U/l. The sensitivity of CRP was 100% as well. Concerning IL-17, its concentrations were higher in patients than in the control group (P < 0.001) in the first 24 h. CONCLUSIONS Plasma concentrations of M65 and the M30/M65 ratio can be useful in predicting the severity of acute pancreatitis as early as 24 h after the onset of symptoms. The rates of IL-17 early in the course of acute pancreatitis are indicative of the disease.
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Affiliation(s)
- Sotirios Vlachos
- Second Department of Surgery, Medical School, Democritus University of Thrace, University Hospital of Alexandroupolis, Alexandroupolis, 68100, Greece; Postgraduate Program in Hepatobiliary/Pancreatic Surgery, Medical School, Democritus University of Thrace, Alexandroupolis, Greece
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Xue P, Guo J, Yang XN, Huang W, Xia Q. Changes of neuronal acetylcholine receptor alpha 7 of peritoneal macrophage in experimental acute pancreatitis treated by Chaiqin Chengqi Decoction (). Chin J Integr Med 2014; 20:770-5. [PMID: 24452489 DOI: 10.1007/s11655-013-1661-x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2011] [Indexed: 02/05/2023]
Abstract
OBJECTIVE To investigate effect of Chaiqin Chengqi Decoction (, CQCQD) on changes of neuronal acetylcholine receptor alpha 7 (nAChRα7) of peritoneal macrophages in acute pancreatitis (AP). METHODS Eighteen Kunming mice were equally randomized into the control group, AP group and CQCQD treatment group. AP was induced by two intraperitoneal injections of 4 g/kg L-arginine at 1 h apart, while control mice received saline injections. At 72 h after the first injection of L-arginine, mice in the treatment group were intragastrically administered 0.1 mL/10 g CQCQD every 2 h for 3 times, whilst mice in the other two groups received the same amount of saline feeding. Mice were sacrificed by cervical dislocation 2 h after the last feeding of either CQCQD or saline. Peritoneal macrophages were collected for determination of nAChRα7 mRNA and protein expression. Serum was collected for detection of interleukin-6 (IL-6), IL-10 and acetylcholine (ACh) levels, and pancreas was for histopathology analysis. RESULTS The CQCQD treatment significantly ameliorated the severity of AP as evidenced by reducing the pancreatic histopathology score (4.5±0.5 vs. 6.2±1.7, P<0.05) and the serum IL-6 levels (1228.3±419.2 pg/mL vs. 1589.6±337.3 pg/mL, P<0.05). The mRNA and protein expression of nAChRα7 of the peritoneal macrophages in the AP group were similar to the control group (P>0.05), but were significantly up-regulated after the CQCQD treatment (P<0.05). The serum ACh levels in the AP group were significantly lower than those in the control group (3.1±0.6 μg/mL vs 4.8±0.7 μg/mL P<0.05), but were significantly increased after the CQCQD treatment (5.6±1.5 μg/mL vs 3.1±0.6 μg/mL, P<0.05). CONCLUSION CQCQD is protective against L-arginine-induced AP through mechanisms involving nAChRα7 of peritoneal macrophages.
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Affiliation(s)
- Ping Xue
- Pancreatic Diseases Research Group, Department of Integrated Traditional and Western Medicine, West China Hospital, Sichuan University, Chengdu, 610041, China
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Influence of interleukin gene polymorphisms on development of acute pancreatitis: a systematic review and meta-analysis. Mol Biol Rep 2013; 40:5931-41. [PMID: 24072654 DOI: 10.1007/s11033-013-2700-6] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2013] [Accepted: 09/14/2013] [Indexed: 02/07/2023]
Abstract
Several epidemiological studies have assessed the associations of interleukin (IL) gene polymorphisms with acute pancreatitis (AP) in different populations. However, the results were inconclusive. Therefore, we performed the present study to comprehensively evaluate the associations of IL gene polymorphisms and susceptibility to AP. Systematic searches of the PubMed, Web of Science, Embase, CNKI, CBMdisc and Google Scholar until February 27, 2013, as well as hand searching of the references of identified articles were performed. Data were extracted using standardized forms and odds ratios (ORs) with 95 % confidence intervals (CIs) were used to assess the strength of associations. All statistical analyses were performed using Stata 11.0. Ten studies were included in our final combined analysis, covering a total of 1,220 AP cases and 1,351 controls. The results showed evidence for significant association between IL-8 -251 T/A (rs4073) polymorphism and AP risk, suggesting that IL-8 -251 A allele was associated with an increased risk of AP (for A allele vs. T allele: OR = 1.36, 95 % CI 1.05-1.76, p = 0.02; for A/A vs. T/T: OR = 2.28, 95 % CI 1.08-4.81, p = 0.03; for A/A+T/A vs. T/T: OR = 1.40, 95 % CI 1.11-1.77, p = 0.005). However, there were no significant associations between IL-1β (IL-1β +3954 C/T (rs1143634) and IL-1β -511 C/T (rs16944)), IL-6 (IL-6 -174 G/C (rs1800795) and IL-6 -634 C/G (rs1800796)) and IL-10 (IL-10 -1082 A/G (rs1800896), IL-10 -819 C/T (rs1800871) and IL-10 -592 C/A (rs1800872)) gene polymorphisms and AP risk. In summary, the current study suggests that the IL-8 -251 T/A polymorphism is associated with an increased risk of AP. In addition, there were no significant associations between IL-1β, IL-6 and IL-10 gene polymorphisms and AP risk.
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Therapeutic effects of electroacupuncture at ST36 acupoint on sodium-taurocholate-induced severe acute pancreatitis. Chin J Integr Med 2013; 20:695-700. [PMID: 23893236 DOI: 10.1007/s11655-013-1331-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2011] [Indexed: 02/05/2023]
Abstract
OBJECTIVE To explore the protective effects and mechanisms of electroacupuncture (EA) at Zusanli (ST36) acupoint in rats with severe acute pancreatitis (SAP). METHODS Sixty-six male Sprague-Dawley rats were randomly assigned to three groups of 22 each: a SAP model group (SAP group), a shamoperated group (sham group) and a EA at ST36 acupoint group (EA group). A rat model of SAP was induced by pancreatic duct injection with 3.5% sodium taurocholate. EA was performed at ST36 acupoint for 30 min after induction of SAP and 30 min before sacrificed. The rats were killed at 3 h (n=7), 6 h (n=7) and 12 h (n=8) after operation, and blood samples were taken for the measurement of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and acetylcholine (Ach) by enzyme-linked immunosorbnent assay. The pathological changes of pancreatic tissue, volume of ascites and pancreatic weight/body weight ratio were measured. RESULTS The serum concentrations of TNF-α and IL-6 in the EA group were significantly lower than in the SAP group at 3, 6 and 12 h after the operation (p<0.05). Serum Ach in the EA group was significantly higher than in the SAP group at various time points after operation (p<0.05). The other parameters were clearly improved after treatment with EA. CONCLUSION EA at ST36 acupoint might have a therapeutic effect in rats with SAP through activating the cholinergic anti-inflammatory pathway.
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The Role of IL-6, 8, and 10, sTNFr, CRP, and Pancreatic Elastase in the Prediction of Systemic Complications in Patients with Acute Pancreatitis. Gastroenterol Res Pract 2013; 2013:282645. [PMID: 23476635 PMCID: PMC3583135 DOI: 10.1155/2013/282645] [Citation(s) in RCA: 65] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2012] [Accepted: 11/26/2012] [Indexed: 12/16/2022] Open
Abstract
Background and Aim. Early assessment of severity in acute pancreatitis (AP) is a key measure to provide rational and effective management. The aim of our study is to determine the prognostic value of interleukins (IL) 6, 8, and 10, soluble receptor for tumor necrosis factor (sTNFr), pancreatic elastase (E1), and C-reactive protein (CRP) as predictors of systemic complications in AP. Patients and Methods. A hundred and fifty patients with confirmed AP were enrolled in the study. The severity of AP was defined according to Atlanta criteria. Measurements of interleukins and sTNFr were performed on the first day of admission. CRP and E1 levels were assessed on admission and after 48 hours. ROC analysis was performed for all parameters. Results. Interleukins and sTNFr significantly differentiated patients with systemic complications from those without. Elevation of IL-6 showed the highest significance as a predictor (P = 0.001). CRP and elastase levels did not differ between mild and severe cases on admission, but reached statistical significance when measured on the third day (P = 0.002 and P = 0.001, resp.). Conclusion. Our study confirmed that IL-6, IL-8, IL-10, and sTNFr measured on admission, and CRP and pancreatic elastase measured on third day of admission represent valuable prognostic factors of severity and systemic complications of AP.
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Involvement of inflammatory factors in pancreatic carcinogenesis and preventive effects of anti-inflammatory agents. Semin Immunopathol 2012; 35:203-27. [PMID: 22955327 DOI: 10.1007/s00281-012-0340-x] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2012] [Accepted: 08/23/2012] [Indexed: 12/13/2022]
Abstract
Chronic inflammation is known to be a risk for many cancers, including pancreatic cancer. Heavy alcohol drinking and cigarette smoking are major causes of pancreatitis, and epidemiological studies have shown that smoking and chronic pancreatitis are risk factors for pancreatic cancer. Meanwhile, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) are elevated in pancreatitis and pancreatic cancer tissues in humans and in animal models. Selective inhibitors of iNOS and COX-2 suppress pancreatic cancer development in a chemical carcinogenesis model of hamsters treated with N-nitrosobis(2-oxopropyl)amine (BOP). In addition, hyperlipidemia, obesity, and type II diabetes are also suggested to be associated with chronic inflammation in the pancreas and involved in pancreatic cancer development. We have shown that a high-fat diet increased pancreatic cancer development in BOP-treated hamsters, along with aggravation of hyperlipidemia, severe fatty infiltration, and increased expression of adipokines and inflammatory factors in the pancreas. Of note, fatty pancreas has been observed in obese and/or diabetic cases in humans. Preventive effects of anti-hyperlipidemic/anti-diabetic agents on pancreatic cancer have also been shown in humans and animals. Taking this evidence into consideration, modulation of inflammatory factors by anti-inflammatory agents will provide useful data for prevention of pancreatic cancer.
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Abstract
OBJECTIVES We aimed at synchronously examining the early time course of 4 proinflammatory cytokines as predictive factors for development of organ failure in patients with acute pancreatitis (AP). METHODS Interleukin (IL) 6, IL-8, IL-18, and tumor necrosis factor α were measured on admission and at days 1, 2, and 14 in 60 patients admitted with first attack of AP. The prediction of single-organ and multiorgan failure from the cytokine profiles was evaluated by receiver operating characteristic analyses. RESULTS Interleukin 6 and IL-8 levels were significantly higher in patients who developed renal, respiratory, and circulatory failure, as was the case for patients with multiorgan failure. Interleukin 18 levels were significantly elevated in renal and respiratory failure only. Tumor necrosis factor α was significantly elevated in all types of organ failures, except for intestinal failure. CONCLUSIONS Synchronous measurements of 4 cytokines demonstrated IL-6 and IL-8 to be predictive as early surrogate markers with regard to organ failures in AP. The fact that all of the cytokines were particularly elevated in patients with organ failures calls for evaluation of agents modifying the severe inflammatory response in patients with AP.
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Abstract
OBJECTIVES Serine Protease Inhibitor Kazal type 1 (SPINK1) protects against premature intracellular activation of trypsinogen and development of acute pancreatitis. Our aim was to determine the prevalence of SPINK1 mutations (a) in unselected patients with first-time acute pancreatitis and (b) in the Danish background population (c) in a meta-analysis to combine the results with findings in similar investigations worldwide and (d) to evaluate whether patients with SPINK1 mutations had a more severe clinical course. METHODS A total of 75 consecutive patients admitted to a surgical department with first-time acute pancreatitis were prospectively included. In addition, 188 healthy controls were tested for the SPINK1 variants: p.N34S, p.P55S, p.R65Q, p.R67C, and IVS3+2 T>C, in order to calculate the prevalence of SPINK1 mutations in the Danish background population. A meta-analysis was conducted on previous studies on acute pancreatitis and SPINK1 mutations. RESULTS Two patients (2.7%) and two controls (1.1%) were heterozygous for the p.N34S variant. The meta-analysis confirmed that the p.N34S variant is overrepresented in patients with acute pancreatitis compared with the background population (OR=3.16, P<0.001). But this analysis did not clarify whether this was only true for patients with first-time acute pancreatitis or recurrent pancreatitis as the present studies do not provide this information, and those who do not have enough patients to reach levels of statistic significance, even if data are pooled. CONCLUSION The SPINK1 variant p.N34S is overrepresented in patients with acute pancreatitis, but more studies distinguishing between first-time and recurrent acute pancreatitis have to be done to determine whether this is only true for patients with recurrent acute pancreatitis.
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Assessment of trypsinogen-2 levels as an early diagnostic for post-endoscopic retrograde cholangiopancreatography pancreatitis. Pancreas 2011; 40:1206-10. [PMID: 21792081 DOI: 10.1097/mpa.0b013e318223d362] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
OBJECTIVES The objective of the present study was to assess the use of serum trypsinogen-2 (TRY-2) measurements in early diagnosis of pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP). METHODS In this prospective study, investigation 1 involved collection of blood serum both before and at 2, 4, and 18 hours after ERCP, whereas investigation 2 involved collection before and 1, 2, 3, 4, 6, and 18 hours after ERCP. Total amylase, pancreatic amylase, and TRY-2 levels were measured from serum samples, and values from patients with pancreatitis after ERCP were compared to those from healthy control patients after ERCP. RESULTS In investigation 1, 8 of the 68 cases examined were diagnosed as post-ERCP pancreatitis. In the healthy group, total- and pancreatic-amylase levels peaked 4 hours after ERCP, and TRY-2 levels peaked at 2 hours after ERCP. In contrast, cases of post-ERCP pancreatitis demonstrated prolonged periods of high total-amylase, pancreatic-amylase, and TRY-2 levels. In investigation 2, none of the 23 cases was diagnosed as post-ERCP pancreatitis: Pancreatic amylase levels peaked 4 to 6 hours after ERCP and TRY-2 levels peaked 1 hour after ERCP. CONCLUSION These results suggest that TRY-2 is a more sensitive marker than amylase, and it can be useful in early diagnosis of post-ERCP pancreatitis.
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Ramudo L, Yubero S, Manso MA, Recio JS, Weruaga E, De Dios I. Effect of dexamethasone on peripheral blood leukocyte immune response in bile-pancreatic duct obstruction-induced acute pancreatitis. Steroids 2010; 75:362-7. [PMID: 20152847 DOI: 10.1016/j.steroids.2010.01.018] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2009] [Revised: 01/22/2010] [Accepted: 01/26/2010] [Indexed: 12/22/2022]
Abstract
Our aim was to analyze the effects of dexamethasone (Dx) (1mg/kg), prophylactically or therapeutically administered, on the inflammatory response triggered by peripheral blood leukocytes during acute pancreatitis (AP) induced in rats by bile-pancreatic duct obstruction (BPDO) and their consequences in the progress of the disease. Flow cytometry was used to analyze the distribution of the major leukocyte populations, the CD45 expression and the activated state of monocytes as reflected by the membrane-bound intercellular adhesion molecule-1 (ICAM-1) and the production of tumor necrosis factor-alpha (TNF-alpha) and monocyte chemoattract protein-1 (MCP-1) in response to lipopolysaccaride (LPS). Interleukin-6 (IL-6) plasma levels, pancreatic fluid content and histology of pancreas sections were also evaluated. Dx, given either before or after AP, blunted the monocyte increase induced by BPDO-induced AP, but did not change lymphocyte and neutrophil counts. Membrane-bound ICAM-1 expression did not vary in circulating monocytes during BPDO, either in Dx-treated or non-treated rats. Both Dx treatments inhibited TNF-alpha and MCP-1 production in non-stimulated and LPS-stimulated monocytes, whose response was found to be higher than in controls from early AP. Leukocyte CD45 expression was found to be reduced in rats with AP and shifted to control values in Dx-post-treated rats. Cytokinemia as well as pancreatic edema and leukocyte infiltration found in BPDO rats were reduced by Dx given either before or after AP. We conclude that prophylactic and therapeutic Dx treatments inhibited the inflammatory response triggered by circulating leukocytes in rats with BPDO-induced AP, thus contributing to reducing the severity of the disease.
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Affiliation(s)
- Laura Ramudo
- Department of Physiology and Pharmacology, University of Salamanca, 37007 Salamanca, Spain
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Aoun E, Chen J, Reighard D, Gleeson FC, Whitcomb DC, Papachristou GI. Diagnostic accuracy of interleukin-6 and interleukin-8 in predicting severe acute pancreatitis: a meta-analysis. Pancreatology 2010; 9:777-85. [PMID: 20110745 DOI: 10.1159/000214191] [Citation(s) in RCA: 77] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2008] [Accepted: 04/09/2009] [Indexed: 12/11/2022]
Abstract
OBJECTIVES The early identification of patients at risk for severe acute pancreatitis (SAP) is crucial. Serum markers of disease severity have been assessed including interleukin (IL)-6 and IL-8; however, their predictive accuracy has varied significantly across studies. We conducted a meta-analysis to assess the accuracy of IL-6 and IL-8 at predicting SAP. METHODS We identified relevant published articles and calculated pooled sensitivities, specificities and likelihood ratios using the random-effect model. We included values for days 1, 2 and 3 of presentation for IL-6 and for days 1 and 2 for IL-8. We also constructed summary receiver-operating curves and assessed the area under the curve (AUC) and the diagnostic odds ratios (DORs) as measures of diagnostic accuracy. RESULTS For IL-6, we included 7 reports for day 1 and 4 reports for days 2 and 3. For IL-8, we analyzed 5 studies for day 1 and 4 for day 2. The pooled IL-6 sensitivities ranged between 81.0 and 83.6% and specificities between 75.6 and 85.3% with positive likelihood ratios of 3.43, 4.90 and 4.40 for days 1, 2 and 3, respectively. The IL-8 pooled sensitivities were 65.8 and 70.9% with specificities of 66.5 and 91.3% for days 1 and 2 with positive likelihood ratios of 1.96 and 8.15. The IL-6 AUCs were 0.75, 0.88 and 0.85 for days 1, 2 and 3. The IL-8 AUCs were 0.73 and 0.91 for days 1 and 2. The DOR for IL-6 was higher than that of IL-8 on day 1. CONCLUSION IL-6 and IL-8 seem to perform at an acceptable level in predicting SAP. Larger confirmatory studies formally comparing this performance with that of more commonly used markers are needed.
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Affiliation(s)
- Elie Aoun
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, Pa., USA
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Serum profiles of C-reactive protein, interleukin-8, and tumor necrosis factor-alpha in patients with acute pancreatitis. HPB SURGERY : A WORLD JOURNAL OF HEPATIC, PANCREATIC AND BILIARY SURGERY 2010; 2009:878490. [PMID: 20130823 PMCID: PMC2814374 DOI: 10.1155/2009/878490] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/10/2009] [Revised: 07/28/2009] [Accepted: 11/16/2009] [Indexed: 12/22/2022]
Abstract
Background-Aims. Early prediction of the severity of acute pancreatitis would lead to prompt intensive treatment resulting in improvement of the outcome. The present study investigated the use of C-reactive protein (CRP), interleukin IL-8 and tumor necrosis factor-α (TNF-α) as prognosticators of the severity of the disease.
Methods. Twenty-six patients with acute pancreatitis were studied. Patients with APACHE II score of 9 or more formed the severe group, while the mild group consisted of patients with APACHE II score of less than 9. Serum samples for measurement of CRP, IL-8 and TNF-α were collected on the day of admission and additionally on the 2nd, 3rd and 7th days.
Results. Significantly higher levels of IL-8 were found in patients with severe acute pancreatitis compared to those with mild disease especially at the 2nd and 3rd days (P = .001 and P = .014, resp.). No significant difference for CRP and TNF-α was observed between the two groups. The optimal cut-offs for IL-8 in order to discriminate severe from mild disease at the 2nd and 3rd days were 25.4 pg/mL and 14.5 pg/mL, respectively.
Conclusions. IL-8 in early phase of acute pancreatitis is superior marker compared to CRP and TNF-α for distinguishing patients with severe disease.
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Duarte-Rojo A, Suazo-Barahona J, Ramírez-Iglesias MT, Uscanga LF, Robles-Díaz G. Time frames for analysis of inflammatory mediators in acute pancreatitis: improving admission triage. Dig Dis Sci 2009; 54:2282-7. [PMID: 19082718 DOI: 10.1007/s10620-008-0615-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2008] [Accepted: 11/03/2008] [Indexed: 12/22/2022]
Abstract
Improving the outcome of acute pancreatitis through prognostic markers has been a matter of ample research. We evaluate the clinical usefulness of four serum markers in comparison to Ranson's score. Serum measurements of C-reactive protein (CRP), interleukin-6, -10 (IL-6, IL-10), and pancreatitis-associated protein (PAP) were performed. The usefulness of each marker for predicting severity was compared with that of Ranson's score. Time of evolution was considered for improving their usefulness. Seventy-one patients were studied. Severe cases had higher levels of all markers, although only IL-10 had better accuracy than Ranson's. In patients admitted during the first 48 h, IL-6, IL-10, and PAP had improved accuracy over Ranson's; however, after this time frame, only CRP outperformed Ranson's score. Analysis of time frames improved the accuracy of all markers. Therefore, time of evolution should be considered when using these parameters for a better prognosis.
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Affiliation(s)
- Andrés Duarte-Rojo
- Pancreatic Unit, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
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Jastrow KM, Gonzalez EA, McGuire MF, Suliburk JW, Kozar RA, Iyengar S, Motschall DA, McKinley BA, Moore FA, Mercer DW. Early cytokine production risk stratifies trauma patients for multiple organ failure. J Am Coll Surg 2009; 209:320-31. [PMID: 19717036 DOI: 10.1016/j.jamcollsurg.2009.05.002] [Citation(s) in RCA: 89] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2009] [Revised: 05/05/2009] [Accepted: 06/05/2009] [Indexed: 01/15/2023]
Abstract
BACKGROUND Shock is a prime inciting event for postinjury multiple organ failure (MOF), believed to induce a state of injurious systemic inflammation. In animal models of hemorrhagic shock, early (< 24 hours) changes in cytokine production are an index of the systemic inflammatory response syndrome. However, their predictive value in trauma patients remains to be fully elucidated. STUDY DESIGN In a prospective observational pilot study of > 1 year at an urban Level I trauma center, serial (every 4 hours) serum cytokine levels were determined during a 24-hour period using multiplex suspension immunoassay in patients with major torso trauma (excluding severe brain injury) who met criteria for standardized shock resuscitation. Temporal cytokine expression was assessed during shock resuscitation in severe trauma patients to predict risk for MOF. MOF was assessed with the Denver score. RESULTS Of 48 study patients (mean age 39 +/- 3 years, 67% men, 88% blunt mechanism, mean Injury Severity Score 25 +/- 2), MOF developed in 11 (23%). MOF patients had a considerably higher mortality (64% versus 3%) and fewer ICU-free days (3.5 +/- 2 versus 17.8 +/- 1.3 days) compared with non-MOF patients. Traditional predictors of MOF, including age (45 +/- 7 versus 38 +/- 3 years; p=0.21), Injury Severity Score (26 +/- 3 versus 25 +/- 2; p=0.67), admission hemoglobin (11.4 +/- 0.9 versus 12.1 +/- 0.5 g/dL; p=0.22), international normalized ratio (1.6 +/- 0.2 versus 1.4 +/- 0.06; p=0.17), and base deficit (9.0 +/- 2 versus 7.1 +/- 0.8; p=0.19), were not significantly different between MOF and non-MOF patients. Statistical analysis identified six candidate predictors of MOF: inducible protein 10, macrophage inflammatory protein-1beta, interleukin-10, interleukin-6, interleukin-1Ra, and eotaxin. CONCLUSIONS These data provide insight into cytokine expression during traumatic shock that can enable earlier identification of patients at risk for development of MOF.
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Affiliation(s)
- Kenneth M Jastrow
- Department of Surgery, University of Texas Medical School at Houston, Houston, TX
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Abstract
Acute pancreatitis has an incidence of about 300 per 1 million individuals per year, of which 10-15% of patients develop the severe form of the disease. Novel management options, which have the potential to improve outcome, include initial proper fluid resuscitation, which maintains microcirculation and thereby potentially decreases ischaemia and reperfusion injury. The traditional treatment concept in acute pancreatitis, fasting and parenteral nutrition, has been challenged and early initiation of enteral feeding in severe pancreatitis and oral intake in mild acute pancreatitis is both feasible and provides some benefits. There are at present no data supporting immunonutritional supplements and probiotics should be avoided in patients with acute pancreatitis. There is also no evidence of any benefits provided by prophylactic antibacterials in patients with predicted severe acute pancreatitis. A variety of specific medical interventions have been investigated (e.g. intense blood glucose monitoring by insulin) but none has become clinically useful. Lessons can probably be learned from critical care in general, but studies are needed to verify these interventions in acute pancreatitis.
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Affiliation(s)
- Roland Andersson
- Department of Surgery, Clinical Sciences Lund, Lund University Hospital, Lund, Sweden.
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Chen WC, Nie JS. Genetic polymorphism of MCP-1-2518, IL-8-251 and susceptibility to acute pancreatitis: a pilot study in population of Suzhou, China. World J Gastroenterol 2008; 14:5744-8. [PMID: 18837094 PMCID: PMC2748212 DOI: 10.3748/wjg.14.5744] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2008] [Revised: 07/22/2008] [Accepted: 07/29/2008] [Indexed: 02/06/2023] Open
Abstract
AIM To study the relationship between MCP-1-2518A/G, IL-8-251A/T polymorphism and acute pancreatitis (AP) in the Han population of Suzhou, China. METHODS A case-control study was conducted to compare the distribution of genotype and genetic frequency of MCP-1-2518A/G, IL-8-251A/T gene polymorphism among AP (n = 101), including mild AP (n = 78) and severe AP (n = 23) and control healthy individuals (n = 120) with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing, and analyze the relationship between the MCP-1-2518A/G, IL-8-251A/T gene polymorphism and the susceptibility to AP. RESULTS Significant differences were found in the distribution of genotype of MCP-1-2518A/G between the healthy control group and mild AP group (chi2 = 32.015, P < 0.001), the same was evident between the healthy control group and severe AP group (chi2 = 12.932, P < 0.05) in Suzhou. However, no difference of genotypic distribution was noted between MAP and SAP (chi2 = 0.006, P = 0.997). The genetic frequencies of G allele in mild AP were 72.4% (113/156) and 76.1% (35/46) in severe AP, both were higher than the controls, 47.1% (113/240) (chi2 = 24.804; P < 0.001, and chi2 = 13.005; P < 0.001), but no difference was found between severe AP and mild AP (chi2 = 0.242; P = 0.623). No difference was found in the distribution of genotype of IL-8-251A/T between the healthy control group and AP group neither in the frequency of A and T allele. CONCLUSION The MCP-1-2518 AA genotype of the population in Suzhou may be a protective genotype of AP, while one with higher frequency of G allele is more likely to suffer from pancreatitis. But the genotype of AA and the frequency of G allele could not predict the risk of severe AP. No correlation is found between the IL-8-251 polymorphism and the liability of AP.
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Abstract
UNLABELLED The circumstances that determine how acute pancreatitis (AP) becomes severe are unknown. Differences in cytokine genetic encoding may determine the severity or influence the etiology of AP. This article investigates the relationship between different polymorphisms of tumor necrosis factor alpha (TNF-alpha), interleukin 1 (IL-1), IL-1 receptor antagonist, IL-6, and IL-10 with the severity and etiology of AP and the serum levels of the cytokine encoded. METHODS Patients with AP were included prospectively. Severity of the disease was determined according to Atlanta classification. Serum levels of these cytokines were determined within the first 72 hours after the onset of symptoms. The following polymorphisms were determined by polymerase chain reaction: IL-1a -889, IL-1b +3954, IL-1b -511, variable number tandem repeats, IL-6 -174, IL-6 -597, IL-10 -592, TNF-alpha 308, TNF-alpha 238, and TNF-B250. RESULTS Eighty-four patients were included. The GA genotype of the TNF-alpha 238 polymorphism was associated with more frequent respiratory failure and shock than the GG genotype. Gallstone pancreatitis was associated with the CC genotype of the IL-6 -174 CC polymorphism. CONCLUSIONS AG genotype of the TNF-alpha 238 polymorphism is associated with organic failure in patients with AP. The CC genotype of the IL-6 174 polymorphism is associated with biliary etiology of acute pancreatitis.
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Abstract
The aim of the present review is to summarize the current knowledge regarding pharmacological prevention and treatment of acute pancreatitis (AP) based on experimental animal models and clinical trials. Somatostatin (SS) and octreotide inhibit the exocrine production of pancreatic enzymes and may be useful as prophylaxis against Post Endoscopic retrograde cholangiopancreatography Pancreatitis (PEP). The protease inhibitor Gabexate mesilate (GM) is used routinely as treatment to AP in some countries, but randomized clinical trials and a meta-analysis do not support this practice. Nitroglycerin (NGL) is a nitrogen oxide (NO) donor, which relaxes the sphincter of Oddi. Studies show conflicting results when applied prior to ERCP and a large multicenter randomized study is warranted. Steroids administered as prophylaxis against PEP has been validated without effect in several randomized trials. The non-steroidal anti-inflammatory drugs (NSAID) indomethacin and diclofenac have in randomized studies showed potential as prophylaxis against PEP. Interleukin 10 (IL-10) is a cytokine with anti-inflammatory properties but two trials testing IL-10 as prophylaxis to PEP have returned conflicting results. Antibodies against tumor necrosis factor-alpha (TNF-α) have a potential as rescue therapy but no clinical trials are currently being conducted. The antibiotics beta-lactams and quinolones reduce mortality when necrosis is present in pancreas and may also reduce incidence of infected necrosis. Evidence based pharmacological treatment of AP is limited and studies on the effect of potent anti-inflammatory drugs are warranted.
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Abstract
The aim of the study was to identify immunohistochemically the localization of interleukin (IL)-6 in normal pancreas and in chronic pancreatitis (CP). Samples of tissues of normal pancreas (n=5) and CP (n=16), were verified histopathologically and then IL-6 was localized by immunohistochemical staining using the monoclonal antihuman IL-6 antibody and test LSAB2-HRP to visualize IL-6/Ab complexes. In slices of the pancreas, derived from patients with CP, a much stronger immunohistochemical reaction was noticed as compared with controls specimens. IL-6 was localized in exocrine, islet cells and ducts cells of the pancreas. Interestingly, this cytokine was detected in cytoplasm and very close to nucleus. Moreover, in cases of CP with inflammatory infiltration, there were a markedly stronger IL-6 expression, than that observed in specimens without infiltrate. In conclusion, the results presented herein clearly demonstrated a moderate and strong expression of IL-6 in exocrine and endocrine cells of patients with CP. These observations provide further support for the existence of local immune-pancreatic interactions.
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Schoenbein C, Docke WD, Wolk K, Belbe G, Hoflich C, Jung M, Grutz G, Sterry W, Volk HD, Asadullah K, Sabat R. Long-term interleukin-10 presence induces the development of a novel, monocyte-derived cell type. Clin Exp Immunol 2008; 151:306-16. [PMID: 18062799 PMCID: PMC2276947 DOI: 10.1111/j.1365-2249.2007.03554.x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/16/2007] [Indexed: 12/22/2022] Open
Abstract
Interleukin (IL)-10 is one of the most crucial immunoregulatory cytokines. Its short-term effects have been analysed extensively, but little is known about its long-term effects. This is of considerable importance, as high systemic IL-10 levels are present for long periods in patients with persistent viral infections, certain cancers and in critical care patients. Our study investigated the effects of the long-term presence of IL-10 on human peripheral blood monocytes. In vitro, IL-10 treatment of these cells for 7 days induced the development of a novel cell type characterized by unique phenotypical and functional characteristics. These cells showed high HLA-DR expression and low expression of CD86 and other co-stimulatory molecules on their surface. The mRNA levels of both HLA-DR and CD86 were high, but no intracellular accumulation of CD86 protein was observed. With respect to its function, these cells showed strongly diminished tumour necrosis factor-alpha production following lipopolysaccharide stimulation, strongly diminished allogenic CD4(+) T cell stimulatory capacity, and even induced a hyporesponsive state in CD4(+) T cells. The phenotype remained stable despite the removal of IL-10. In vivo, we found monocytic cells from patients exhibiting this phenotype after long-term IL-10 exposure. These results complement our knowledge further about the biological effects of IL-10 and may provide an explanation for the sustained immunodeficiency in cases of the persistent presence of systemic IL-10.
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Affiliation(s)
- C Schoenbein
- Interdisciplinary Group of Molecular Immunopathology, Dermatology/Medical Immunology, University Hospital Charité, Berlin, Germany
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Dimopoulou I, Orfanos S, Kotanidou A, Livaditi O, Giamarellos-Bourboulis E, Athanasiou C, Korovesi I, Sotiropoulou C, Kopterides P, Ilias I, Kanellakopoulou K, Armaganidis A. Plasma pro- and anti-inflammatory cytokine levels and outcome prediction in unselected critically ill patients. Cytokine 2008; 41:263-7. [PMID: 18191577 DOI: 10.1016/j.cyto.2007.11.019] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2007] [Revised: 10/23/2007] [Accepted: 11/30/2007] [Indexed: 12/22/2022]
Abstract
PURPOSE To determine the inter-relationships between cytokine levels and physiological scores in predicting outcome in unselected, critically ill patients. METHODS To this end, 127 patients (96 men), having a mean+/-SD age of 45+/-20 years, with a wide range in admission diagnoses (medical, surgical, and multiple trauma patients) were prospectively investigated. Severity of critical illness and organ dysfunction were graded by acute physiology and chronic health evaluation (APACHE II) and sequential organ failure assessment (SOFA) scores, respectively. Blood samples were drawn on admission in the ICU to determine pro- and anti-inflammatory cytokines, including tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-8, and IL-10. The main outcome measure was 28-day mortality. RESULTS Overall, 88 patients survived and 39 patients died. Univariate logistic regression analysis showed that SOFA, APACHE II, IL-8, IL-6, and IL-10 on admission in the ICU were related to mortality. Multiple logistic regression analysis in the entire cohort of critically ill patients revealed that SOFA (OR=1.341, p<0.001) and IL-6 (OR=1.075, p=0.01) constituted independent outcome predictors. receiver operator characteristics curve analysis showed that SOFA, APACHE II, and IL-6 had the highest area under the curve values. IL-6 correlated with APACHE II (r(s)=0.44, p<0.0001) and SOFA (r(s)=0.40, p<0.0001) scores. CONCLUSIONS In mixed ICU patients cytokine concentrations on admission in the ICU represent independent outcome predictors in the presence of disease severity scores.
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Affiliation(s)
- Ioanna Dimopoulou
- Second Department of Critical Care Medicine, Attikon Hospital, Medical School, University of Athens, 2 Pesmazoglou Street, 14 561 Kifissia, Athens, Greece.
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48
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Andersson R, Eckerwall G, Axelsson J. Clinical Research in Acute Pancreatitis and the Failure to Predict Severe Disease. Ann Surg 2007; 246:689-690. [DOI: 10.1097/sla.0b013e318156e2a8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Wolk K, Höflich C, Zuckermann-Becker H, Döcke WD, Volk HD, Sabat R. Reduced monocyte CD86 expression in postinflammatory immunodeficiency. Crit Care Med 2007; 35:458-67. [PMID: 17204999 DOI: 10.1097/01.ccm.0000254724.54515.2f] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
OBJECTIVE Major surgery, polytrauma, stroke, and pancreatitis frequently lead to a compensatory anti-inflammatory response syndrome that often predisposes patients to lethal infections. This temporary postinflammatory immunodeficiency is characterized by altered function of blood monocytes. These cells show strongly reduced inflammatory and antigen-presentation capacity. Diminished monocyte expression of the major histocompatibility complex class II molecule human leukocyte antigen (HLA)-DR is a well-established diagnostic marker of this immunodeficiency. To further characterize the monocytic cells in this clinical state, we analyzed their expression of CD86, the most important co-stimulatory molecule. DESIGN Analysis of blood samples that entered the clinical immunologic diagnostics and of cells from an in vitro model of postinflammatory immunodeficiency. SETTING University laboratory. SUBJECTS Healthy donors and intensive care unit (ICU) patients at the university hospital. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS The expression of HLA-DR on monocytes and of CD86 and CD80 on monocytes and B cells was analyzed by flow cytometry. Messenger RNA expression of CD86 was analyzed in isolated monocytes by real-time polymerase chain reaction on reverse transcribed. The normal range of monocyte CD86 expression in healthy subjects was established to be from 2128 to 5102 surface molecules per cell and was independent of age, gender, and leukocyte and monocyte count. The CD86 expression on monocytes in ICU patients correlated with HLA-DR expression. Approximately 40% of the ICU patients with long-term reduced monocyte HLA-DR expression had a long-term reduction of CD86 expression. Patients in whom the expression of both molecules was diminished had an unfavorable prognosis. The diminished number of CD86 surface molecules on monocytes was associated with reduced CD86 messenger RNA levels in these cells. The expression of CD86 in B cells was not diminished in immunodeficient patients. The expression of CD80 in both monocytes and B-cells was minimal in healthy donors and not clearly changed in patients. CONCLUSIONS The monocyte CD86 expression may be a helpful diagnostic variable in ICU patients.
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Affiliation(s)
- Kerstin Wolk
- Institute of Medical Immunology and Department of General, Visceral, Vascular, Thoracic Surgery, University Hospital Charité, Berlin, Germany
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Panek J, Karcz D, Pieton R, Zasada J, Tusinski M, Dolecki M, Winiarski M. Blood serum levels of proinflammatory cytokines in patients with different degrees of biliary pancreatitis. CANADIAN JOURNAL OF GASTROENTEROLOGY = JOURNAL CANADIEN DE GASTROENTEROLOGIE 2007; 20:645-8. [PMID: 17066155 PMCID: PMC2660792 DOI: 10.1155/2006/372892] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
BACKGROUND Proinflammatory cytokines play a fundamental role in the local and systemic inflammatory responses in the initial stages of acute biliary pancreatitis (ABP) and in the development of severe forms of the disease. OBJECTIVES The aim of the present study was to assess the systemic release of proinflammatory cytokines and to characterize differences between patients with mild ABP (MABP) and severe ABP (SABP). PATIENTS AND METHODS In the current study, 54 patients with MABP were compared with 14 patients with SABP. Serum levels of tumour necrosis factor-alpha, interleukin (IL)-1beta, IL-6, IL-8 and IL-12p40 were measured every second day after admission for one week. RESULTS The tumour necrosis factor-alpha level was similar in all days of analysis in patients with MABP but was lower compared with SABP patients. The level of IL-1beta was higher at admission in patients with MABP. The level of IL-6 peaked on admission day in both groups, but in patients with SABP, the obtained values were higher. The level of IL-8 on admission day was slightly higher in patients with MABP and systematically decreased when measured on the following days (the third, fifth and seventh days of the study). An increased level of IL-8 during the third, fifth and seventh days of the investigation was seen in SABP patients. The level of IL-12p40 was slightly higher in patients with MABP on the day of admission. CONCLUSIONS The levels of some proinflammatory cytokines are higher in patients with SABP than in patients with MABP. The most consistent difference between the two groups was that the levels of IL-6 were significantly higher in patients with SABP throughout the study. Serum concentration of IL-6 may be helpful as a marker of severity and outcome of ABP.
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Affiliation(s)
- Józefa Panek
- Second Department of Surgery, Collegium Medicum of Jagiellonian University, Kraków, Poland.
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