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Rafaqat S, Azam A, Hafeez R, Faseeh H, Tariq M, Asif M, Arshad A, Noshair I. Role of interleukins in the pathogenesis of coronary heart disease: A literature review. World J Cardiol 2025; 17:103947. [PMID: 40161563 PMCID: PMC11947956 DOI: 10.4330/wjc.v17.i3.103947] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2024] [Revised: 01/22/2025] [Accepted: 02/10/2025] [Indexed: 03/21/2025] Open
Abstract
Interleukins (ILs), a subset of cytokines, play a critical role in the pathogenesis of coronary heart disease (CHD) by mediating inflammation. This review article summarizes the role of ILs such as IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, and IL-10 in the pathogenesis of CHD. Individuals with mild coronary artery disease (CAD) and angina who have ischemic heart disease have higher serum concentrations of IL-1b. Larger studies are needed to verify the safety and assess the effectiveness of low-dose IL-2 as an anti-inflammatory treatment. IL-3 is found more often in patients receiving coronary angioplasty compared to patients with asymptomatic CAD or without CAD. Serum levels of IL-4 are reliable indicators of CAD. An independent correlation between IL-5 and the incidence of CAD was demonstrated. IL-6 helps serve as a reliable biomarker for the degree of CAD, as determined by the Gensini score, and is a key factor in the development of atherosclerosis. Also, variants of IL-7/7R have been linked to the Han Chinese population's genetic susceptibility to CHD. IL-8 plays a role in the progression of CAD occurrences. By interacting with conventional risk factors for CAD, IL-9 may contribute to the development of CAD and offer an innovative approach to its prevention and management. There was a 34% increased risk of a CHD incident for every standard deviation rise in baseline IL-10 levels.
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Affiliation(s)
- Saira Rafaqat
- Department of Zoology (Molecular Physiology), Lahore College for Women University, Lahore 54000, Pakistan.
| | - Azeem Azam
- Institute of Zoology, University of the Punjab, Lahore 54000, Pakistan
| | - Ramsha Hafeez
- Department of Zoology (Molecular Physiology), Lahore College for Women University, Lahore 54000, Pakistan
| | - Hamza Faseeh
- Department of Zoology, Govt. Islamia Graduate College Civil Lines, Lahore 54000, Pakistan
| | - Maria Tariq
- Department of Zoology, University of Education, Lahore 54000, Pakistan
| | - Muhammad Asif
- Department of Zoology, University of Education, Lahore 54000, Pakistan
| | - Amber Arshad
- Department of Zoology (Molecular Physiology), Lahore College for Women University, Lahore 54000, Pakistan
| | - Iqra Noshair
- Department of Zoology (Molecular Physiology), Lahore College for Women University, Lahore 54000, Pakistan
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Watrowski R, Schuster E, Polterauer S, Van Gorp T, Hofstetter G, Fischer MB, Mahner S, Zeillinger R, Obermayr E. Genetic Variants of Interleukin-8 and Interleukin-16 and Their Association with Cervical Cancer Risk. Life (Basel) 2025; 15:135. [PMID: 40003544 PMCID: PMC11856530 DOI: 10.3390/life15020135] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Revised: 12/22/2024] [Accepted: 01/18/2025] [Indexed: 02/27/2025] Open
Abstract
BACKGROUND Cervical cancer (CC) is the fourth most common cancer diagnosis in women worldwide. Infection with high-risk human papillomavirus (HPV) is a critical but not determinative condition for CC development, as several co-factors modulate the progression of HPV-associated cervical lesions. Interleukin-8 (IL-8) and Interleukin-16 (IL-16) are chemokine-like interleukins involved in the pathogenesis of various cancers. Singular studies in Asian populations have suggested a potential role of IL-8 rs4073 (-251 A>T) and IL-16 rs1131445 (3'UTR T>C) in cervical carcinogenesis. METHODS A case-control study was conducted in a European cohort of 339 women, including 126 CC patients and 213 controls. Four common IL-8 SNPs, rs4073 (-251 A>T), rs2227306 (+781 C>T), rs1126647 (+2767 A>T), and rs2227543 (+1633 C>T), and four IL-16 polymorphism, rs4778889 (-295 T>C), rs11556218 (3441 T>G), rs4072111 (1300 C>T), and rs1131445 (3'UTR T>C), were assessed using RFLP-PCR and analyzed under seven inheritance models. Subgroup analyses were stratified by menopausal status (age threshold 51 years), disease stage, and histological subtype. RESULTS IL-16 rs4072111 was significantly associated with an increased CC risk in premenopausal women in the co-dominant (p = 0.038), dominant (p = 0.022), and heterozygote (p = 0.045) models, identifying the T allele as the risk allele (OR 2.31, CI95% 1.17-4.56; p = 0.017). In women aged over 51, IL-16 rs4778889 was associated with CC in the heterozygote (p = 0.048) and overdominant (p = 0.042) models but not in the co-dominant model (p = 0.092). None of the analyzed SNPs significantly increased CC risk in the entire cohort. Specifically, neither IL-16 rs1131445 nor IL-8 rs4073, previously reported as risk factors in Asian populations, were associated with CC risk in this European cohort. CONCLUSIONS These findings highlight the role of age stage in immunity and cancer susceptibility, suggest that IL-8 and IL-16 SNPs may function differently in cervical carcinogenesis compared with other cancers, and emphasize the importance of ethnic background in cancer risk, warranting further research.
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Affiliation(s)
- Rafał Watrowski
- Department of Obstetrics and Gynecology, Helios Hospital Muellheim, Teaching Hospital of the University of Freiburg, Heliosweg 1, 79379 Muellheim, Germany;
- Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany
| | - Eva Schuster
- Molecular Oncology Group, Department of Obstetrics and Gynecology, Comprehensive Cancer Center-Gynecologic Cancer Unit, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria; (E.S.); (S.P.); (R.Z.)
| | - Stefan Polterauer
- Molecular Oncology Group, Department of Obstetrics and Gynecology, Comprehensive Cancer Center-Gynecologic Cancer Unit, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria; (E.S.); (S.P.); (R.Z.)
| | - Toon Van Gorp
- Division of Gynecologic Oncology, University Hospital Leuven, 3000 Leuven, Belgium;
- Leuven Cancer Institute, Catholic University of Leuven, 3000 Leuven, Belgium
| | - Gerda Hofstetter
- Department of Pathology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria;
| | - Michael B. Fischer
- Department of Blood Group Serology and Transfusion Medicine, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria;
- Center for Biomedical Technology, Department for Biomedical Research, Danube University Krems, Dr.-Karl-Dorrek-Straße 30, 3500 Krems, Austria
| | - Sven Mahner
- Department of Gynecology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany;
- Department of Obstetrics and Gynecology, University Hospital, Ludwig-Maximilians-University Munich, 81377 Munich, Germany
| | - Robert Zeillinger
- Molecular Oncology Group, Department of Obstetrics and Gynecology, Comprehensive Cancer Center-Gynecologic Cancer Unit, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria; (E.S.); (S.P.); (R.Z.)
| | - Eva Obermayr
- Molecular Oncology Group, Department of Obstetrics and Gynecology, Comprehensive Cancer Center-Gynecologic Cancer Unit, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria; (E.S.); (S.P.); (R.Z.)
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Li F, Zhang Y, Wang Y, Cai X, Fan X. Cytokine Gene Variants as Predisposing Factors for the Development and Progression of Coronary Artery Disease: A Systematic Review. Biomolecules 2024; 14:1631. [PMID: 39766338 PMCID: PMC11726869 DOI: 10.3390/biom14121631] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2024] [Revised: 12/12/2024] [Accepted: 12/16/2024] [Indexed: 01/04/2025] Open
Abstract
Coronary artery disease (CAD) is the most prevalent form of cardiovascular disease. A growing body of research shows that interleukins (ILs), such as IL-8, IL-18 and IL-16, elicit pro-inflammatory responses and may play critical roles in the pathologic process of CAD. Single nucleotide polymorphisms (SNPs), capable of generating functional modifications in IL genes, appear to be associated with CAD risk. This study aims to evaluate the associations of ten previously identified SNPs of the three cytokines with susceptibility to or protection of CAD. A systematic review and meta-analysis were conducted using Pubmed, EMBASE, WOS, CENTRAL, CNKI, CBM, Weipu, WANFANG Data and Google Scholar databases for relevant literature published up to September 2024. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for the four genetic models of the investigated SNPs in overall and subgroups analyses. Thirty-eight articles from 16 countries involving 14574 cases and 13001 controls were included. The present meta-analysis revealed no significant association between CAD and IL-8-rs2227306 or five IL-16 SNPs (rs8034928, rs3848180, rs1131445, rs4778889 and rs11556218). However, IL-8-rs4073 was significantly associated with an increased risk of CAD across all genetic models. In contrast, three IL-18 (rs187238, rs1946518 and rs1946519) variants containing minor alleles were associated with decreased risks of CAD under all models. Subgroups analyses by ethnicity indicated that IL-8-rs4073 conferred a significantly higher risk of CAD among Asians, including East, South and West Asians (allelic OR = 1.46, homozygous OR = 1.96, heterozygous OR = 1.47, dominant OR = 1.65), while it showed an inversely significant association with CAD risk in Caucasians (homozygous OR = 0.82, dominant OR = 0.85). Additionally, IL-18-rs187238 and IL-18-rs1946518 were significantly associated with reduced CAD risks in East Asians (for rs187238: allelic OR = 0.72, homozygous OR = 0.33, heterozygous OR = 0.73, dominant OR = 0.71; for rs1946518: allelic OR = 0.62, homozygous OR = 0.38, heterozygous OR = 0.49, dominant OR = 0.45). IL-18-rs187238 also demonstrated protective effects in Middle Eastern populations (allelic OR = 0.76, homozygous OR = 0.63, heterozygous OR = 0.72, dominant OR = 0.71). No significant associations were observed in South Asians or Caucasians for these IL-18 SNPs. Consistent with the overall analysis results, subgroups analyses further highlighted a significant association between IL-8-rs4073 and increased risk of acute coronary syndrome (heterozygous OR = 0.72). IL-18-rs187238 was significantly associated with decreased risks of myocardial infarction (MI) (allelic OR = 0.81, homozygous OR = 0.55, dominant OR = 0.80) and multiple vessel stenosis (allelic OR = 0.54, heterozygous OR = 0.45, dominant OR = 0.45). Similarly, IL-18-rs1946518 was significantly associated with reduced MI risk (allelic OR = 0.75, heterozygous OR = 0.68). These findings support the role of cytokine gene IL-8 and IL-18 variants as predisposing factors for the development and progression of CAD.
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Affiliation(s)
- Fang Li
- Correspondence: (F.L.); (X.F.); Tel.: +86-731-88872780 (F.L. & X.F.)
| | | | | | | | - Xiongwei Fan
- The Laboratory of Heart Development Research, College of Life Sciences, Hunan Normal University, Changsha 410081, China; (Y.Z.); (Y.W.); (X.C.)
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Băghină RM, Crișan S, Luca S, Pătru O, Lazăr MA, Văcărescu C, Negru AG, Luca CT, Gaiță D. Association between Inflammation and New-Onset Atrial Fibrillation in Acute Coronary Syndromes. J Clin Med 2024; 13:5088. [PMID: 39274304 PMCID: PMC11396258 DOI: 10.3390/jcm13175088] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2024] [Revised: 08/23/2024] [Accepted: 08/26/2024] [Indexed: 09/16/2024] Open
Abstract
Acute coronary syndrome (ACS) is a complex clinical syndrome that encompasses acute myocardial infarction (AMI) and unstable angina (UA). Its underlying mechanism refers to coronary plaque disruption, with consequent platelet aggregation and thrombosis. Inflammation plays an important role in the progression of atherosclerosis by mediating the removal of necrotic tissue following myocardial infarction and shaping the repair processes that are essential for the recovery process after ACS. As a chronic inflammatory disorder, atherosclerosis is characterized by dysfunctional immune inflammation involving interactions between immune (macrophages, T lymphocytes, and monocytes) and vascular cells (endothelial cells and smooth muscle cells). New-onset atrial fibrillation (NOAF) is one of the most common arrhythmic complications in the setting of acute coronary syndromes, especially in the early stages, when the myocardial inflammatory reaction is at its maximum. The main changes in the atrial substrate are due to atrial ischemia and acute infarcts that can be attributed to neurohormonal factors. The high incidence of atrial fibrillation (AF) post-myocardial infarction may be secondary to inflammation. Inflammatory response and immune system cells have been involved in the initiation and development of atrial fibrillation. Several inflammatory indexes, such as C-reactive protein and interleukins, have been demonstrated to be predictive of prognosis in patients with ACS. The cell signaling activation patterns associated with fibrosis, apoptosis, and hypertrophy are forms of cardiac remodeling that occur at the atrial level, predisposing to AF. According to a recent study, the presence of fibrosis and lymphomononuclear infiltration in the atrial tissue was associated with a prior history of AF. However, inflammation may contribute to both the occurrence/maintenance of AF and its thromboembolic complications.
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Affiliation(s)
- Ruxandra-Maria Băghină
- Cardiology Department, "Victor Babes" University of Medicine and Pharmacy, 2 Eftimie Murgu Sq., 300041 Timisoara, Romania
- Institute of Cardiovascular Diseases Timisoara, 13A Gheorghe Adam Street, 300310 Timisoara, Romania
- Research Center of the Institute of Cardiovascular Diseases Timisoara, 13A Gheorghe Adam Street, 300310 Timisoara, Romania
| | - Simina Crișan
- Cardiology Department, "Victor Babes" University of Medicine and Pharmacy, 2 Eftimie Murgu Sq., 300041 Timisoara, Romania
- Institute of Cardiovascular Diseases Timisoara, 13A Gheorghe Adam Street, 300310 Timisoara, Romania
- Research Center of the Institute of Cardiovascular Diseases Timisoara, 13A Gheorghe Adam Street, 300310 Timisoara, Romania
| | - Silvia Luca
- Cardiology Department, "Victor Babes" University of Medicine and Pharmacy, 2 Eftimie Murgu Sq., 300041 Timisoara, Romania
- Institute of Cardiovascular Diseases Timisoara, 13A Gheorghe Adam Street, 300310 Timisoara, Romania
- Research Center of the Institute of Cardiovascular Diseases Timisoara, 13A Gheorghe Adam Street, 300310 Timisoara, Romania
| | - Oana Pătru
- Cardiology Department, "Victor Babes" University of Medicine and Pharmacy, 2 Eftimie Murgu Sq., 300041 Timisoara, Romania
- Research Center of the Institute of Cardiovascular Diseases Timisoara, 13A Gheorghe Adam Street, 300310 Timisoara, Romania
| | - Mihai-Andrei Lazăr
- Cardiology Department, "Victor Babes" University of Medicine and Pharmacy, 2 Eftimie Murgu Sq., 300041 Timisoara, Romania
- Institute of Cardiovascular Diseases Timisoara, 13A Gheorghe Adam Street, 300310 Timisoara, Romania
- Research Center of the Institute of Cardiovascular Diseases Timisoara, 13A Gheorghe Adam Street, 300310 Timisoara, Romania
| | - Cristina Văcărescu
- Cardiology Department, "Victor Babes" University of Medicine and Pharmacy, 2 Eftimie Murgu Sq., 300041 Timisoara, Romania
- Institute of Cardiovascular Diseases Timisoara, 13A Gheorghe Adam Street, 300310 Timisoara, Romania
- Research Center of the Institute of Cardiovascular Diseases Timisoara, 13A Gheorghe Adam Street, 300310 Timisoara, Romania
| | - Alina Gabriela Negru
- Cardiology Department, "Victor Babes" University of Medicine and Pharmacy, 2 Eftimie Murgu Sq., 300041 Timisoara, Romania
- Institute of Cardiovascular Diseases Timisoara, 13A Gheorghe Adam Street, 300310 Timisoara, Romania
- Research Center of the Institute of Cardiovascular Diseases Timisoara, 13A Gheorghe Adam Street, 300310 Timisoara, Romania
| | - Constantin-Tudor Luca
- Cardiology Department, "Victor Babes" University of Medicine and Pharmacy, 2 Eftimie Murgu Sq., 300041 Timisoara, Romania
- Institute of Cardiovascular Diseases Timisoara, 13A Gheorghe Adam Street, 300310 Timisoara, Romania
- Research Center of the Institute of Cardiovascular Diseases Timisoara, 13A Gheorghe Adam Street, 300310 Timisoara, Romania
| | - Dan Gaiță
- Cardiology Department, "Victor Babes" University of Medicine and Pharmacy, 2 Eftimie Murgu Sq., 300041 Timisoara, Romania
- Institute of Cardiovascular Diseases Timisoara, 13A Gheorghe Adam Street, 300310 Timisoara, Romania
- Research Center of the Institute of Cardiovascular Diseases Timisoara, 13A Gheorghe Adam Street, 300310 Timisoara, Romania
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Watrowski R, Schuster E, Hofstetter G, Fischer MB, Mahner S, Van Gorp T, Polterauer S, Zeillinger R, Obermayr E. Association of Four Interleukin-8 Polymorphisms (-251 A>T, +781 C>T, +1633 C>T, +2767 A>T) with Ovarian Cancer Risk: Focus on Menopausal Status and Endometriosis-Related Subtypes. Biomedicines 2024; 12:321. [PMID: 38397923 PMCID: PMC10886609 DOI: 10.3390/biomedicines12020321] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2023] [Revised: 01/22/2024] [Accepted: 01/27/2024] [Indexed: 02/25/2024] Open
Abstract
Interleukin-8 (IL-8) is involved in the regulation of inflammatory processes and carcinogenesis. Single-nucleotide polymorphisms (SNPs) within the IL-8 gene have been shown to alter the risks of lung, gastric, or hepatocellular carcinomas. To date, only one study examined the role of IL-8 SNPs in ovarian cancer (OC), suggesting an association between two IL-8 SNPs and OC risk. In this study, we investigated four common IL-8 SNPs, rs4073 (-251 A>T), rs2227306 (+781 C>T), rs2227543 (+1633 C>T), and rs1126647 (+2767 A>T), using the restriction fragment length polymorphism (PCR-RFLP) technique. Our study included a cohort of 413 women of Central European descent, consisting of 200 OC patients and 213 healthy controls. The most common (73.5%) histological type was high-grade serous OC (HGSOC), whereas 28/200 (14%) patients had endometriosis-related (clear cell or endometrioid) OC subtypes (EROC). In postmenopausal women, three of the four investigated SNPs, rs4073 (-251 A>T), rs2227306 (+781 C>T), and rs2227543 (+1633 C>T), were associated with OC risk. Furthermore, we are the first to report a significant relationship between the T allele or TT genotype of SNP rs1126647 (+2767 A>T) and the EROC subtype (p = 0.02 in the co-dominant model). The TT homozygotes were found more than twice as often in EROC compared to other OC subtypes (39% vs. 19%, p = 0.015). None of the examined SNPs appeared to influence OC risk in premenopausal women, nor were they associated with the aggressive HGSOC subtype or the stage of disease at the initial diagnosis.
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Affiliation(s)
- Rafał Watrowski
- Department of Obstetrics and Gynecology, Helios Hospital Muellheim, Teaching Hospital of the University of Freiburg, Heliosweg 1, 79379 Muellheim, Germany;
- Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany;
- Molecular Oncology Group, Department of Obstetrics and Gynecology, Comprehensive Cancer Center-Gynaecologic Cancer Unit, Medical University of Vienna, Waehringer Guertel 18–20, 1090 Vienna, Austria; (E.S.); (R.Z.)
| | - Eva Schuster
- Molecular Oncology Group, Department of Obstetrics and Gynecology, Comprehensive Cancer Center-Gynaecologic Cancer Unit, Medical University of Vienna, Waehringer Guertel 18–20, 1090 Vienna, Austria; (E.S.); (R.Z.)
| | - Gerda Hofstetter
- Department of Pathology, Medical University of Vienna, Waehringer Guertel 18–20, 1090 Vienna, Austria;
| | - Michael B. Fischer
- Department of Blood Group Serology and Transfusion Medicine, Medical University of Vienna, Waehringer Guertel 18–20, 1090 Vienna, Austria;
- Center for Biomedical Technology, Department for Biomedical Research, Danube University Krems, Dr.-Karl-Dorrek-Straße 30, 3500 Krems, Austria
| | - Sven Mahner
- Department of Gynaecology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany;
- Department of Obstetrics and Gynaecology, University Hospital, Ludwig-Maximilians-University Munich, 81377 Munich, Germany
| | - Toon Van Gorp
- Division of Gynaecologic Oncology, University Hospital Leuven, 3000 Leuven, Belgium;
- Leuven Cancer Institute, Catholic University of Leuven, 3000 Leuven, Belgium
| | - Stefan Polterauer
- Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany;
| | - Robert Zeillinger
- Molecular Oncology Group, Department of Obstetrics and Gynecology, Comprehensive Cancer Center-Gynaecologic Cancer Unit, Medical University of Vienna, Waehringer Guertel 18–20, 1090 Vienna, Austria; (E.S.); (R.Z.)
| | - Eva Obermayr
- Molecular Oncology Group, Department of Obstetrics and Gynecology, Comprehensive Cancer Center-Gynaecologic Cancer Unit, Medical University of Vienna, Waehringer Guertel 18–20, 1090 Vienna, Austria; (E.S.); (R.Z.)
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Pan K, Xu C, Chen C, Chen S, Zhang Y, Ding X, Xu X, Lv Q. Soluble interleukin-2 receptor combined with interleukin-8 is a powerful predictor of future adverse cardiovascular events in patients with acute myocardial infarction. Front Cardiovasc Med 2023; 10:1110742. [PMID: 37139133 PMCID: PMC10150071 DOI: 10.3389/fcvm.2023.1110742] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Accepted: 03/21/2023] [Indexed: 05/05/2023] Open
Abstract
Background Little is known about the role of interleukin (IL) in patients with acute myocardial infarction (MI), especially soluble IL-2 receptor (sIL-2R) and IL-8. We aim to evaluate, in MI patients, the predictive value of serum sIL-2R and IL-8 for future major adverse cardiovascular events (MACEs), and compare them with current biomarkers reflecting myocardial inflammation and injury. Methods This was a prospective, single-center cohort study. We measured serum concentrations of IL-1β, sIL-2R, IL-6, IL-8 and IL-10. Levels of current biomarkers for predicting MACEs were measured, including high-sensitivity C reactive protein, cardiac troponin T and N-terminal pro-brain natriuretic peptide. Clinical events were collected during 1-year and a median of 2.2 years (long-term) follow-up. Results Twenty-four patients (13.8%, 24/173) experienced MACEs during 1-year follow-up and 40 patients (23.1%, 40/173) during long-term follow-up. Of the five interleukins studied, only sIL-2R and IL-8 were independently associated with endpoints during 1-year or long-term follow-up. Patients with high sIL-2R or IL-8 levels (higher than the cutoff value) had a significantly higher risk of MACEs during 1-year (sIL-2R: HR 7.7, 3.3-18.0, p < 0.001; IL-8: HR 4.8, 2.1-10.7, p < 0.001) and long-term (sIL-2R: HR 7.7, 3.3-18.0, p < 0.001; IL-8: HR 4.8, 2.1-10.7, p < 0.001) follow-up. Receiver operator characteristic curve analysis regarding predictive accuracy for MACEs during 1-year follow-up showed that the area under the curve for sIL-2R, IL-8, sIL-2R combined with IL-8 was 0.66 (0.54-0.79, p = 0.011), 0.69 (0.56-0.82, p < 0.001) and 0.720 (0.59-0.85, p < 0.001), whose predictive value were superior to that of current biomarkers. The addition of sIL-2R combined with IL-8 to the existing prediction model resulted in a significant improvement in predictive power (p = 0.029), prompting a 20.8% increase in the proportion of correct classifications. Conclusions High serum sIL-2R combined with IL-8 levels was significantly associated with MACEs during follow-up in patients with MI, suggesting that sIL-2R combined with IL-8 may be a helpful biomarker for identifying the increased risk of new cardiovascular events. IL-2 and IL-8 would be promising therapeutic targets for anti-inflammatory therapy.
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Affiliation(s)
- Kunming Pan
- Department of Pharmacy, Zhongshan Hospital Fudan University, Shanghai, China
| | - Chenqi Xu
- Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China
- Shanghai Institute of Kidney Disease and Dialysis, Shanghai, China
- Shanghai Key Laboratory of Kidney and Blood Purification, Shanghai, China
- Shanghai Medical Center of Kidney Disease, Shanghai, China
| | - Can Chen
- Department of Pharmacy, Zhongshan Hospital Fudan University, Shanghai, China
| | - Shuqing Chen
- School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yuqian Zhang
- Department of Pharmacy, Zhongshan Hospital Fudan University, Shanghai, China
| | - Xiaoqiang Ding
- Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China
- Shanghai Institute of Kidney Disease and Dialysis, Shanghai, China
- Shanghai Key Laboratory of Kidney and Blood Purification, Shanghai, China
- Shanghai Medical Center of Kidney Disease, Shanghai, China
| | - Xialian Xu
- Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China
- Shanghai Institute of Kidney Disease and Dialysis, Shanghai, China
- Shanghai Key Laboratory of Kidney and Blood Purification, Shanghai, China
- Shanghai Medical Center of Kidney Disease, Shanghai, China
- Correspondence: Qianzhou Lv Xialian Xu
| | - Qianzhou Lv
- Department of Pharmacy, Zhongshan Hospital Fudan University, Shanghai, China
- Correspondence: Qianzhou Lv Xialian Xu
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Zhang Q, Lian Z, Zhang W, Cui Y, Wang W, Wu J, Chen Z, Wang W. Association between interleukin-8 gene -251 A/T polymorphism and the risk of coronary artery disease: A meta-analysis. Medicine (Baltimore) 2019; 98:e17866. [PMID: 31770200 PMCID: PMC6890313 DOI: 10.1097/md.0000000000017866] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
BACKGROUND The association between interleukin-8 (IL-8) gene polymorphism -251 A>T and susceptibility to coronary artery disease (CAD) has been investigated previously; however, results remain controversial. Thus, a meta-analysis was conducted to reassess the effects of this polymorphism on CAD risks. METHODS The PubMed, Cochrane Library, China National Knowledge Infrastructure, and Wanfang databases were searched for relevant studies published up to December, 2018. The pooled odds ratios (OR) were calculated using STATA 13.0 software for allelic (A vs T) as well as homozygote (AA vs TT), heterozygote (AT vs TT), recessive (AA vs AT + TT), and dominant (AA + AT vs TT) genotype models, respectively. RESULTS Ten case-control studies (3744 cases and 3660 controls) were included. Overall, a significant association of IL-8 gene -251 A > T polymorphism with an increased risk of CAD was only observed in the dominant genotype model (OR = 1.48), but not others. In the subgroup analysis, significantly increased risks were also found for Chinese (OR = 1.64), polymerase chain reaction-restriction fragment length polymorphism genotyping (OR = 1.61), acute coronary syndrome (ACS) type (OR = 1.92 for 3 datasets; OR = 1.88 for 4 datasets), high quality (OR = 1.64), and age/gender matching status (OR = 1.55) under the dominant model. Furthermore, significantly increased risks were also found for ACS type under allelic (OR = 1.32 for 3 datasets; OR = 127 for 4 datasets), homozygote (OR = 1.64 for 3 datasets; OR = 1.50 for 4 datasets), heterozygote (OR = 1.32 for 3 datasets; OR = 1.30 for 4 datasets), and recessive (OR = 1.40 for 3 datasets; OR = 1.28 for 4 datasets) models. CONCLUSION This meta-analysis suggests that Chinese patients carrying -251A allele of IL-8 may have an increased risk for the development of CAD, especially ACS.
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Affiliation(s)
| | | | | | | | | | - Jun Wu
- Department of Gastroenterology
| | | | - Wei Wang
- Department of Pharmacy, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China
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Li Y, Bai J, He B, Wang N, Wang H, Liu D. Weak association between the interleukin-8 rs4073 polymorphism and acute pancreatitis: a cumulative meta-analysis. BMC MEDICAL GENETICS 2019; 20:129. [PMID: 31340771 PMCID: PMC6657145 DOI: 10.1186/s12881-019-0861-4] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/28/2019] [Accepted: 07/17/2019] [Indexed: 12/24/2022]
Abstract
Background Several studies have been performed to investigate the associations between interleukin (IL)-8 rs4073 polymorphism and acute pancreatitis (AP), but the results are inconclusive. We conducted this cumulative meta-analysis for a precise estimate of the relationship between IL-8 rs4073 polymorphism and acute pancreatitis. Methods We searched the electronic databases for relevant studies. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the associations. For a better presentation of how the pooled ORs changed as updated evidence accumulated, we used forest plots from a cumulative meta-analysis method. Results Ten studies involving 1646 AP patients and 1816 controls were finally included in this meta-analysis. Cumulative meta-analyses indicated there is a consistent trend toward association after the initial discovery. Under the allelic, dominant, recessive and homozygous models, the pooled ORs were 1.265 (1.147–1.395, p < 0.001), 1.304 (1.127–1.508, p < 0.001), 1.431 (1.203–1.702, p < 0.001), and 1.634 (1.334–2.001, p < 0.001), respectively. Conclusions This meta-analysis demonstrated a suggestive result that people who carried the risk A allele of the IL-8 rs4073 polymorphism may be more sensitive to acute pancreatitis. Electronic supplementary material The online version of this article (10.1186/s12881-019-0861-4) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Yening Li
- Cardiovascular Institute of Luohe and Departments of Intense Care Unit (YL), Endocrinology (JB), Arthritis Surgery (BH), Pediatrics (NW) and Cardiology (HW and DL), Luohe Central Hospital, Luohe Medical College, 56# Renmin Ave, Luohe, 462000, People's Republic of China
| | - Jing Bai
- Cardiovascular Institute of Luohe and Departments of Intense Care Unit (YL), Endocrinology (JB), Arthritis Surgery (BH), Pediatrics (NW) and Cardiology (HW and DL), Luohe Central Hospital, Luohe Medical College, 56# Renmin Ave, Luohe, 462000, People's Republic of China
| | - Bing He
- Cardiovascular Institute of Luohe and Departments of Intense Care Unit (YL), Endocrinology (JB), Arthritis Surgery (BH), Pediatrics (NW) and Cardiology (HW and DL), Luohe Central Hospital, Luohe Medical College, 56# Renmin Ave, Luohe, 462000, People's Republic of China
| | - Nan Wang
- Cardiovascular Institute of Luohe and Departments of Intense Care Unit (YL), Endocrinology (JB), Arthritis Surgery (BH), Pediatrics (NW) and Cardiology (HW and DL), Luohe Central Hospital, Luohe Medical College, 56# Renmin Ave, Luohe, 462000, People's Republic of China
| | - Haoran Wang
- Cardiovascular Institute of Luohe and Departments of Intense Care Unit (YL), Endocrinology (JB), Arthritis Surgery (BH), Pediatrics (NW) and Cardiology (HW and DL), Luohe Central Hospital, Luohe Medical College, 56# Renmin Ave, Luohe, 462000, People's Republic of China.
| | - Dongliang Liu
- Cardiovascular Institute of Luohe and Departments of Intense Care Unit (YL), Endocrinology (JB), Arthritis Surgery (BH), Pediatrics (NW) and Cardiology (HW and DL), Luohe Central Hospital, Luohe Medical College, 56# Renmin Ave, Luohe, 462000, People's Republic of China
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Bartekova M, Radosinska J, Jelemensky M, Dhalla NS. Role of cytokines and inflammation in heart function during health and disease. Heart Fail Rev 2019; 23:733-758. [PMID: 29862462 DOI: 10.1007/s10741-018-9716-x] [Citation(s) in RCA: 178] [Impact Index Per Article: 29.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
By virtue of their actions on NF-κB, an inflammatory nuclear transcription factor, various cytokines have been documented to play important regulatory roles in determining cardiac function under both physiological and pathophysiological conditions. Several cytokines including TNF-α, TGF-β, and different interleukins such as IL-1 IL-4, IL-6, IL-8, and IL-18 are involved in the development of various inflammatory cardiac pathologies, namely ischemic heart disease, myocardial infarction, heart failure, and cardiomyopathies. In ischemia-related pathologies, most of the cytokines are released into the circulation and serve as biological markers of inflammation. Furthermore, there is an evidence of their direct role in the pathogenesis of ischemic injury, suggesting cytokines as potential targets for the development of some anti-ischemic therapies. On the other hand, certain cytokines such as IL-2, IL-4, IL-6, IL-8, and IL-10 are involved in the post-ischemic tissue repair and thus are considered to exert beneficial effects on cardiac function. Conflicting reports regarding the role of some cytokines in inducing cardiac dysfunction in heart failure and different types of cardiomyopathies seem to be due to differences in the nature, duration, and degree of heart disease as well as the concentrations of some cytokines in the circulation. In spite of extensive research work in this field of investigation, no satisfactory anti-cytokine therapy for improving cardiac function in any type of heart disease is available in the literature.
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Affiliation(s)
- Monika Bartekova
- Institute for Heart Research, Centre of Experimental Medicine, Slovak Academy of Sciences, Bratislava, Slovak Republic.,Institute of Physiology, Faculty of Medicine, Comenius University in Bratislava, Bratislava, Slovak Republic
| | - Jana Radosinska
- Institute for Heart Research, Centre of Experimental Medicine, Slovak Academy of Sciences, Bratislava, Slovak Republic.,Institute of Physiology, Faculty of Medicine, Comenius University in Bratislava, Bratislava, Slovak Republic
| | - Marek Jelemensky
- Institute for Heart Research, Centre of Experimental Medicine, Slovak Academy of Sciences, Bratislava, Slovak Republic
| | - Naranjan S Dhalla
- Institute of Cardiovascular Sciences, St. Boniface Hospital Albrechtsen Research Center, 351 Tache Avenue, Winnipeg, MB, R2H 2A6, Canada. .,Department of Physiology and Pathophysiology, Max Rady College of Medicine, University of Manitoba, Winnipeg, Canada.
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Zhang S, Gao Y, Huang J. Interleukin-8 Gene -251 A/T (rs4073) Polymorphism and Coronary Artery Disease Risk: A Meta-Analysis. Med Sci Monit 2019; 25:1645-1655. [PMID: 30826813 PMCID: PMC6410608 DOI: 10.12659/msm.913591] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Inflammation plays an important role in the pathogenesis of coronary artery disease (CAD). Studies have reported that inflammatory cytokine interleukin-8 (IL-8) gene -251 A/T (rs4073) polymorphism is correlated with CAD susceptibility, but the result remains controversial. The objective of this study was to clarify the association between IL-8 gene -251 A/T polymorphism and CAD risk. MATERIAL AND METHODS A meta-analysis included 8244 patients from 9 individual studies with 10 populations was conducted. Heterogeneity test was conducted, and pooled odds ratio (OR) with 95% confidence interval (CI) was calculated used fixed-effect or random-effects model accordingly. Publication bias was evaluated with the Begg's funnel plot and Egger's test. Sensitivity analysis was also conducted. RESULTS A significant association between IL-8 gene -251 A/T polymorphism and CAD risk was found in the dominant model (OR 1.42, 95% CI 1.16-1.76, P<0.001), recessive model (OR 1.30, 95% CI 1.12-1.52, P<0.001), allelic model (OR 1.28, 95% CI 1.12-1.47, P<0.001), homozygote model (OR 1.59, 95% CI 1.21-2.08, P<0.001), and heterozygote model (OR 1.35, 95% CI 1.11-1.64, P=0.002). Subgroup analysis by ethnicity found significant associations in the Chinese population in the dominant model(OR 1.43, 95% CI 1.26-1.61, P<0.001), recessive model (OR 1.39, 95% CI 1.21-1.59, P<0.001), allelic model (OR 1.31, 95% CI 1.21-1.42, P<0.001), homozygote model (OR 1.66, 95% CI 1.41-1.95, P<0.001), and heterozygote model (OR 1.34, 95% CI 1.18-1.52, P<0.001), but no significant association was found in the Caucasian population. No significant publication bias was found. CONCLUSIONS The IL-8 gene -251 A/T polymorphism was significantly associated with CAD risk in the Chinese population but not in the Caucasian population, -251 A allele carrier had an increased risk of CAD in the Chinese population.
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Affiliation(s)
- Shunrong Zhang
- Department of Gerontology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China (mainland)
| | - Yue Gao
- Department of Gerontology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China (mainland)
| | - Jinyu Huang
- Department of Cardiology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China (mainland)
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Wu Y, Wang W, Li XY, Qian LL, Dang SP, Tang X, Chen HJ, Wang RX. Strong association between the interleukin-8-251A/T polymorphism and coronary artery disease risk. Medicine (Baltimore) 2019; 98:e14715. [PMID: 30855465 PMCID: PMC6417535 DOI: 10.1097/md.0000000000014715] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
Several reports have suggested a possible association between the interleukin (IL)-8-251A/T single-nucleotide polymorphism (SNP) and the susceptibility to coronary artery disease (CAD). Due to inconclusive results of the studies so far, we conducted a meta-analysis to systematically summarize the studies on the association between this SNP and CAD risk. A systematic literature search identified 9 case-control studies (3752 cases and 4219 controls) on the IL-8-251A/T polymorphism. We observed a significant association between different genetic forms of -251A/T SNP and CAD risk, like the allele model (A vs T: odds ratio [OR] 1.14, 95% confidence interval [CI] 1.02-1.27, P = .02), dominant model (AA + AT vs TT: OR 1.20, 95% CI 1.01-1.43, P = .042), recessive model (AA vs AT + TT: OR 1.15, 95% CI 1.03-1.27, P = .01), and homozygous model (AA vs TT: OR 1.26, 95% CI 1.01-1.56, P = .037), whereas the heterozygote model did not show any significant association (AT vs TT: OR 1.16, 95% CI 0.98-1.38, P = .091). Furthermore, significant heterogeneity was observed among studies in terms of all genetic models, except the recessive model. Analysis of the ethnic subgroups revealed a significantly higher risk of CAD in the East Asian population carrying this SNP, and the heterogeneity among the studies regarding the East Asian population was decreased after subgroup analysis. The results of this meta-analysis suggest that the IL-8-251A/T SNP may increase the risk of CAD, especially in people of East Asian ethnicity. Further large-scale, multicenter epidemiological studies are warranted to validate this finding.
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Affiliation(s)
- Ying Wu
- Department of Cardiology, Wuxi People's Hospital Affiliated to Nanjing Medical University
| | - Wei Wang
- Wuxi Center for Disease Control and Prevention, Wuxi, Jiangsu, China
| | - Xiao-Yan Li
- Department of Cardiology, Wuxi People's Hospital Affiliated to Nanjing Medical University
| | - Ling-Ling Qian
- Department of Cardiology, Wuxi People's Hospital Affiliated to Nanjing Medical University
| | - Shi-peng Dang
- Department of Cardiology, Wuxi People's Hospital Affiliated to Nanjing Medical University
| | - Xu Tang
- Department of Cardiology, Wuxi People's Hospital Affiliated to Nanjing Medical University
| | - Heng-Jian Chen
- Department of Cardiology, Wuxi People's Hospital Affiliated to Nanjing Medical University
| | - Ru-Xing Wang
- Department of Cardiology, Wuxi People's Hospital Affiliated to Nanjing Medical University
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12
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Wang Z, Gao ZM, Huang HB, Sun LS, Sun AQ, Li K. Association of IL-8 gene promoter -251 A/T and IL-18 gene promoter -137 G/C polymorphisms with head and neck cancer risk: a comprehensive meta-analysis. Cancer Manag Res 2018; 10:2589-2604. [PMID: 30127645 PMCID: PMC6089118 DOI: 10.2147/cmar.s165631] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023] Open
Abstract
Purpose No consensus exists on the impact of polymorphisms in cytokines (such as interleukin IL-8 and IL-18) on cancer risk; moreover, there is very little evidence regarding head and neck cancer (HNC). Methods Thus, a meta-analysis including 22 studies with 4731 cases and 8736 controls was conducted to evaluate this association. The summary odds ratio (OR) and corresponding 95% confidence intervals (CIs) for C-X-C motif chemokine ligand 8 (CXCL8, which encodes IL-8) and IL-18 polymorphisms and HNC risk were estimated. Results The results showed a significantly increased risk of HNC susceptibility for IL18 −137 G/C in five genetic models, but, interestingly, no significant association was found for the CXCL8 −251 A/T polymorphism. When stratified by cancer type, an increased risk of nasopharyngeal cancer was found for both −137 G/C and −251A/T. When the studies were stratified by ethnicity and genotyping method, there were significant associations between Asian populations and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) studies for −137 G/C, and African populations for −251 A/T in some genetic models. A positive association was also found between the population-based groups in some models for −137 G/C; conversely, significantly decreased risk was found among the −251 A/T hospital-based group. Meta-regression was also conducted. The publication year, control source, and cancer type contributed to CXCL8 −251 A/T heterogeneity; however, no factors were found that contributed to IL-18 −137 G/C heterogeneity. Marginal significance was found in the recessive model for IL-18 −137 G/C by Egger’s test, whereas no publication bias was detected for CXCL8 −251 A/T. Conclusions The results indicate that the IL-18 −137 G/C polymorphism is associated with HNC risk, especially nasopharyngeal cancer, in Asian populations and, when using PCR-RFLP, CXCL8 −251 A/T polymorphisms play a complex role in HNC development.
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Affiliation(s)
- Zheng Wang
- Department of Otorhinolaryngology, the First Affiliated Hospital of China Medical University, Shenyang 110001, China
| | - Zi-Ming Gao
- Department of Surgical Oncology, the First Affiliated Hospital of China Medical University, Shenyang 110001, China,
| | - Hai-Bo Huang
- Department of Surgical Oncology, the First Affiliated Hospital of China Medical University, Shenyang 110001, China,
| | - Li-Sha Sun
- Department of Surgical Oncology, the First Affiliated Hospital of China Medical University, Shenyang 110001, China,
| | - An-Qi Sun
- Department of Surgical Oncology, the First Affiliated Hospital of China Medical University, Shenyang 110001, China,
| | - Kai Li
- Department of Surgical Oncology, the First Affiliated Hospital of China Medical University, Shenyang 110001, China,
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13
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Kaur N, Singh J, Reddy S. Association of IL-8-251 A/T rs4073 and IL-10 rs1800872 -592C/A Polymorphisms and Coronary Artery Disease in North Indian Population. Biochem Genet 2018; 57:129-146. [DOI: 10.1007/s10528-018-9880-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2017] [Accepted: 07/20/2018] [Indexed: 12/26/2022]
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Cavusoglu E, Marmur JD, Yanamadala S, Chopra V, Hegde S, Nazli A, Singh KP, Zhang M, Eng C. Elevated baseline plasma IL-8 levels are an independent predictor of long-term all-cause mortality in patients with acute coronary syndrome. Atherosclerosis 2015; 242:589-94. [DOI: 10.1016/j.atherosclerosis.2015.08.022] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2015] [Revised: 08/12/2015] [Accepted: 08/14/2015] [Indexed: 10/23/2022]
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15
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Jian K, Wang Q, Jiang L, Guo Z, Jiang N, Wang L, Liu J. WITHDRAWN: Association between interleukin 8 -251 A/T and +781 C/T polymorphisms and coronary artery disease risk. Hum Immunol 2015:S0198-8859(15)00489-9. [PMID: 26429308 DOI: 10.1016/j.humimm.2015.09.052] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2014] [Revised: 08/17/2014] [Accepted: 09/28/2015] [Indexed: 11/19/2022]
Affiliation(s)
- KaiTao Jian
- Department of Cardiac Surgery, Tianjin Chest Hospital, Tianjin Medical University, Tianjin 300222, China
| | - Qiang Wang
- Department of Cardiac Surgery, Tianjin Chest Hospital, Tianjin Medical University, Tianjin 300222, China
| | - Li Jiang
- Department of Cardiac Surgery, Tianjin Chest Hospital, Tianjin Medical University, Tianjin 300222, China
| | - ZhiGang Guo
- Department of Cardiac Surgery, Tianjin Chest Hospital, Tianjin Medical University, Tianjin 300222, China
| | - Nan Jiang
- Department of Cardiac Surgery, Tianjin Chest Hospital, Tianjin Medical University, Tianjin 300222, China
| | - Lianqun Wang
- Department of Cardiac Surgery, Tianjin Chest Hospital, Tianjin Medical University, Tianjin 300222, China
| | - JianShi Liu
- Department of Cardiac Surgery, Tianjin Chest Hospital, Tianjin Medical University, Tianjin 300222, China.
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Janelidze S, Suchankova P, Ekman A, Erhardt S, Sellgren C, Samuelsson M, Westrin A, Minthon L, Hansson O, Träskman-Bendz L, Brundin L. Low IL-8 is associated with anxiety in suicidal patients: genetic variation and decreased protein levels. Acta Psychiatr Scand 2015; 131:269-78. [PMID: 25251027 DOI: 10.1111/acps.12339] [Citation(s) in RCA: 55] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/28/2014] [Indexed: 12/21/2022]
Abstract
OBJECTIVE Recent studies indicate that inflammation may play a role in the pathophysiology of suicidality. Interleukin-8 (IL-8) is a chemokine that in addition to its function in the immune system also exert neuroprotective properties. The involvement of this chemokine in neuropsychiatric conditions is incompletely known. METHOD We measured plasma and cerebrospinal fluid (CSF) IL-8, as well as the genotype frequency of a single nucleotide polymorphism (-251A/T, rs4073) in the promoter region of the IL8 gene, in suicide attempters (n=206) and healthy controls (n=578). RESULTS Plasma and CSF levels of IL-8 were significantly lower in suicide attempters with anxiety than in healthy controls. IL-8 in both plasma and CSF correlated negatively with symptoms of anxiety. Compared with the population-based cohort, the IL-8-251T allele was more prevalent among female suicide attempters. Furthermore, suicide attempters carrying this allele showed more severe anxiety. This correlative study warrants further mechanistic studies on the effects of IL-8 in the central nervous system. CONCLUSION We suggest that IL-8 might be involved in the biological mechanisms mediating resilience to anxiety. Thus, our findings highlight the chemokine IL-8 as a potential target for future development of anti-anxiety treatments and suicide prevention.
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Affiliation(s)
- S Janelidze
- Section for Psychiatry, Department of Clinical Sciences, Lund University, Lund, Sweden
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Association between interleukin 8 -251 A/T and +781 C/T polymorphisms and osteoarthritis risk. Immunol Lett 2014; 162:207-11. [PMID: 25194757 DOI: 10.1016/j.imlet.2014.08.018] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2014] [Revised: 07/24/2014] [Accepted: 08/08/2014] [Indexed: 11/23/2022]
Abstract
PURPOSE Interleukin 8 (IL-8), as a member of the CXC chemokine family, has a regulatory role in joint inflammation and cartilage degradation, and contribute to the pathophysiology of osteoarthritis. The aim of the current study was to examine the influence of the IL-8 gene polymorphisms at positions -251 (rs4073) and +781 (rs2227306) on the risk of osteoarthritis. METHODS This hospital-based case-control study comprised 150 patients with osteoarthritis and 150 age- and gender-matched controls. IL-8 251 A/T and +781 C/T polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS Patients with osteoarthritis had a significantly higher frequency of IL-8 -251 TT genotype [odds ratio (OR)=2.16, 95% confidence interval (CI)=1.09, 4.26; P=0.03], IL-8 -251 T allele (OR=1.41, 95% CI=1.02, 1.94; P=0.04), IL-8 +781 TT genotype (OR=2.79, 95% CI=1.10, 7.08; P=0.03) and IL-8 +781 T allele (OR=1.48, 95% CI=1.02, 2.14; P=0.04) than controls. But the findings are less emphatic by the Bonferroni correction. When stratifying by body mass index, type, articular involvement, and Kellgren-Lawrence grade, no significant differences were found in any groups. CONCLUSIONS For the first time, the current data suggested that the TT genotype and T allele of the IL-8 gene polymorphisms at positions -251 and +781 might confer a high risk of osteoarthritis. In the future, additional well-designed large studies were required for the validation of our results.
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Velásquez IM, Frumento P, Johansson K, Berglund A, de Faire U, Leander K, Gigante B. Association of interleukin 8 with myocardial infarction: results from the Stockholm Heart Epidemiology Program. Int J Cardiol 2014; 172:173-8. [PMID: 24462138 DOI: 10.1016/j.ijcard.2013.12.170] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2013] [Accepted: 12/31/2013] [Indexed: 11/30/2022]
Abstract
BACKGROUND Interleukin 8 (IL8) has been contradictorily associated with the risk of myocardial infarction (MI). AIM To investigate the association of IL8 serum levels with the risk of MI and the association of the IL8 (IL8) and IL8 receptors (CXCR1 and CXCR2) genetic variants with IL8 levels and MI risk in a large case control study, the Stockholm Heart Epidemiology Program. METHODS AND RESULTS IL8 levels (pg/mL) were divided into quartiles and the MI risk was calculated by logistic regression and expressed as odds ratio (OR) and 95% CI. Two IL8 SNPs (rs4073A/T, rs2227306C/T) and three SNPs tagging CXCR1 and CXCR2 (rs4674258C/T, rs1008563C/T, rs6723449T/C) were analyzed for association with IL8 levels and with MI risk. Multivariate adjusted ORs for MI risk by IL8 levels in the highest quartiles indicated reduced point estimates in both women (OR 0.37; 95% CI 0.2-0.8) and men when compared to the lowest quartile. In female cases, IL8 levels decreased progressively in the six months after MI (p=0.03). IL8, CXCR1 and CXCR2 genetic variants were not associated with IL8 levels. In men, the T allele at the IL8 SNP rs4073 was associated with a slight increase in the MI risk under an additive and a recessive model of inheritance. CONCLUSIONS IL8 serum levels were associated with a reduced occurrence of MI among women, whereas IL8 was associated with a slightly increased risk among men, possibly through different mechanisms. These data suggest that the biological effects of IL8 on MI risk may vary over time and warrant further cohort studies with repetitive IL8 measurements.
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Affiliation(s)
- Ilais Moreno Velásquez
- Unit of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
| | - Paolo Frumento
- Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Katarina Johansson
- Division of Biochemistry, Department of Medical Biochemistry and Biophysics all at Karolinska Institutet, Stockholm, Sweden
| | - Anita Berglund
- Unit of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Ulf de Faire
- Unit of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Dept of Cardiology, Karolinska University Hospital, Stockholm, Sweden
| | - Karin Leander
- Unit of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Bruna Gigante
- Unit of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Division of Cardiovascular Medicine, Dept of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden
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Wacharasint P, Nakada TA, Boyd JH, Russell JA, Walley KR. AA genotype of IL-8 -251A/T is associated with low PaO(2)/FiO(2) in critically ill patients and with increased IL-8 expression. Respirology 2013; 17:1253-60. [PMID: 22897124 DOI: 10.1111/j.1440-1843.2012.02244.x] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND OBJECTIVE Interleukin-8 (IL-8) is a central chemokine in acute respiratory distress syndrome (ARDS), and the IL-8 gene contains a functional single nucleotide polymorphism (SNP) -251A/T in its promoter region. We hypothesized that IL-8 -251A/T SNP is associated with PaO(2)/FiO(2) in critically ill patients. METHODS We conducted genetic-association studies in intensive care units at academic teaching centres using a derivation septic shock cohort (vasopressin and septic shock trial (VASST), n = 467) and a validation post-cardiopulmonary bypass surgery cohort (CPB, n = 739) of Caucasian patients. Patients in both cohorts were genotyped for IL-8 -251A/T. The primary outcome variable in both cohorts was the fraction of patients who had a PaO(2) /FiO(2) < 200. IL-8 mRNA expression was measured in genotyped lymphoblastoid cells in vitro. RESULTS The frequency of the patients with PaO(2)/FiO(2) <200 was significantly greater in patients who had the AA genotype of -251A/T than in patients who had the AT or TT genotypes in both VASST (AA = 60.8% vs AT and TT = 53.8% and 48.0%, P = 0.038) and the CPB cohort (AA = 37.0% vs AT and TT = 27.0% and 26.0%, P = 0.039). Patients having the AA genotype had a higher probability to remain on mechanical ventilation (P = 0.047) in the first 14 days. Lymphoblastoid cells having the AA genotype had significantly higher IL-8 mRNA expression than cells having the AT or TT genotype (P = 0.022). CONCLUSIONS Critically ill Caucasian patients who had the AA genotype of IL-8 -251A/T had an increased risk of PaO(2)/FiO(2) <200. The AA genotype was associated with greater IL-8 mRNA expression than the AT or TT genotypes.
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Affiliation(s)
- Petch Wacharasint
- University of British Columbia, Critical Care Research Laboratories, Institute for Heart+Lung Health, St. Paul's Hospital, Vancouver, BC, Canada
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Blanchet X, Langer M, Weber C, Koenen RR, von Hundelshausen P. Touch of chemokines. Front Immunol 2012; 3:175. [PMID: 22807925 PMCID: PMC3394994 DOI: 10.3389/fimmu.2012.00175] [Citation(s) in RCA: 89] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2012] [Accepted: 06/09/2012] [Indexed: 01/13/2023] Open
Abstract
Chemoattractant cytokines or chemokines constitute a family of structurally related proteins found in vertebrates, bacteria, or viruses. So far, 48 chemokine genes have been identified in humans, which bind to around 20 chemokine receptors. These receptors belong to the seven transmembrane G-protein-coupled receptor family. Chemokines and their receptors were originally studied for their role in cellular trafficking of leukocytes during inflammation and immune surveillance. It is now known that they exert different functions under physiological conditions such as homeostasis, development, tissue repair, and angiogenesis but also under pathological disorders including tumorigenesis, cancer metastasis, inflammatory, and autoimmune diseases. Physicochemical properties of chemokines and chemokine receptors confer the ability to homo- and hetero-oligomerize. Many efforts are currently performed in establishing new therapeutically compounds able to target the chemokine/chemokine receptor system. In this review, we are interested in the role of chemokines in inflammatory disease and leukocyte trafficking with a focus on vascular inflammatory diseases, the operating synergism, and the emerging therapeutic approaches of chemokines.
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Affiliation(s)
- Xavier Blanchet
- Institute for Cardiovascular Prevention, Ludwig-Maximilians-University of Munich Munich, Germany
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Association of systemic inflammation markers with the presence and extent of coronary artery calcification. Cytokine 2011; 57:251-7. [PMID: 22172511 DOI: 10.1016/j.cyto.2011.11.015] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2011] [Revised: 11/15/2011] [Accepted: 11/20/2011] [Indexed: 11/20/2022]
Abstract
BACKGROUND Coronary artery calcification (CAC) is a marker for the presence and extent of coronary atherosclerotic plaques and can be detected non-invasively by multi-detector row CT (MDCT). Well known predictors of CAC are age, gender, and the classical atherogenic risk factors. CAC is associated with atherosclerotic plaque burden, but it is still elusive if atherosclerosis-relevant cytokines and chemokines are also associated with CAC. METHODS We conducted a clinical study among 455 consecutive individuals who underwent coronary calcium assessment performed by MDCT. Before MDCT, blood was drawn and subsequently analyzed for 20 different atherosclerosis-relevant cytokines and chemokines using a Luminex-laser-based fluorescence analysis. RESULTS Using univariate analyses, CAC patients revealed significantly higher levels of the chemokines IP-10 (P=0.047) and eotaxin (P=0.031) as compared to non-CAC patients. In multivariate analyses using common thresholds for calcium burden, the three cytokines interleukin-6 (P=0.028), interleukin-8 (P=0.009), and interleukin-13 (P=0.024) were associated with high coronary calcium levels after adjustment for classical variables and risk factors. CONCLUSIONS In a large group of individuals with atypical chest pain and a low to intermediate likelihood for coronary artery disease elevated plasma levels of IL-6 and reduced levels of IL-8 and IL-13 were predictive for distinct coronary artery calcification. These findings support a specific role of these cytokines in coronary calcification.
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