• cytokines
• inflammation
• interleukin receptors
• interleukins
• liver fibrosis

• Humans
• Liver Cirrhosis/immunology
• Liver Cirrhosis/metabolism
• Liver Cirrhosis/etiology
• Liver Cirrhosis/pathology
• Animals
• Interleukins/metabolism
• Interleukins/immunology
• Liver/immunology
• Liver/pathology
• Liver/metabolism
• Hepatic Stellate Cells/immunology
• Hepatic Stellate Cells/metabolism

• Biological markers
• Interleukin-21
• Interleukin-22
• Interleukin-31
• Liver failure
• Potential value

• HIV-HBV co-infection
• RT-PCR
• antiretroviral treatment
• biomarkers
• ddPCR
• pathogenesis
• public health

• HIV
• SARS-CoV-2
• TGF-β1
• ToRCH
• Zika
• influenza
• pregnancy
• rubella
• transforming growth factor
• virus

Interleukin 31 belongs to the IL-6 superfamily, and it is an itch mediator already studied in several diseases, comprising atopic dermatitis, allergic pathologies, and onco-hematological conditions. This research aims to assess the role of this cytokine in the pathogenesis of these conditions and its potential therapeutic role. The research has been conducted on articles, excluding reviews and meta-analysis, both on animals and humans. The results showed that IL-31 plays a crucial role in the pathogenesis of systemic skin manifestations, prognosis, and itch severity. Traditional therapies target this interleukin indirectly, but monoclonal antibodies (Mab) directed against it have shown efficacy and safety profiles comparable with biological drugs that are already available. Future perspectives could include the development of new antibodies against IL-31 both for humans and animals, thus adding a new approach to the therapy, which often has proven to be prolonged and specific for each patient.

• IL-31
• allergic diseases
• biological drugs
• cancer
• hematological diseases
• interleukin-31
• interleukins
• itch
• respiratory diseases
• skin diseases

Systemic sclerosis (SSc) is a chronic multisystem disorder characterized by fibrosis and autoimmunity. Interleukin (IL)-31 has been implicated in fibrosis and T helper (Th) 2 immune responses, both of which are characteristics of SSc. The exact role of IL-31 in SSc pathogenesis is unclear. Here we show the overexpression of IL-31 and IL-31 receptor A (IL-31RA) in dermal fibroblasts (DFs) from SSc patients. We elucidate the dual role of IL-31 in SSc, where IL-31 directly promotes collagen production in DFs and indirectly enhances Th2 immune responses by increasing pro-Th2 cytokine expression in DFs. Furthermore, blockade of IL-31 with anti-IL-31RA antibody significantly ameliorates fibrosis and Th2 polarization in a mouse model of SSc. Therefore, in addition to defining IL-31 as a mediator of fibrosis and Th2 immune responses in SSc, our study provides a rationale for targeting the IL-31/IL-31RA axis in the treatment of SSc.

Systemic sclerosis (SSc) disease involves multisystem fibrosis and autoimmunity with limited treatment options. Here the authors demonstrate that IL-31 and IL-31RA are overexpressed in dermal fibroblasts from SSc patients and show that fibrosis and cytokine release can be reduced upon blocking of IL-31/IL-31RA.

• Biomarker
• Cirrhosis
• Hepatitis B virus
• Liver
• Long non-coding RNA

The immunopathogenesis and molecular mechanisms involved during a hepatitis B virus (HBV) infection have made the approaches for research complex, especially concerning the patients’ responses in the course of the early acute stage. The study of molecular bases involved in the viral clearance or persistence of the infection is complicated due to the difficulty to detect patients at the most adequate points of the disease, especially in the time lapse between the onset of the infection and the viral emergence. Despite this, there is valuable data obtained from animal and in vitro models, which have helped to clarify some aspects of the early immune response against HBV infection. The diversity of the HBV (genotypes and variants) has been proven to be associated not only with the development and outcome of the disease but also with the response to treatments. That is why factors involved in the virus evolution need to be considered while studying hepatitis B infection. This review brings together some of the published data to try to explain the immunological and molecular mechanisms involved in the different stages of the infection, clinical outcomes, viral persistence, and the impact of the variants of HBV in these processes.

• HBV interference
• HBV sensing
• HBV variability
• acute hepatitis B
• acute liver failure
• chronic hepatitis B
• immune pathogenesis

• Animals
• Genetic Variation
• Genotype
• Hepatitis B/genetics
• Hepatitis B/immunology
• Hepatitis B/pathology
• Hepatitis B/virology
• Hepatitis B virus/classification
• Hepatitis B virus/genetics
• Hepatitis B virus/immunology
• Hepatitis B, Chronic/genetics
• Hepatitis B, Chronic/immunology
• Hepatitis B, Chronic/pathology
• Hepatitis B, Chronic/virology
• Humans
• Virus Replication/genetics
• Virus Replication/immunology

• IL-31
• Th2 cell
• atopic dermatitis
• dendritic cell
• itch
• macrophage
• nemolizumab
• prurigo nodularis
• pruritus

Idiopathic Pulmonary Fibrosis (IPF) is a severe fibrotic lung disease characterized by excessive collagen deposition and progressive decline in lung function. Th2 T cell-derived cytokines including IL-4 and IL-13 have been shown to contribute to inflammation and fibrotic remodeling in multiple tissues. Interleukin-31 (IL-31) is a newly identified cytokine that is predominantly produced by CD4 Th2 T cells, but its signaling receptor IL-31RA is primarily expressed by non-hematopoietic cells. However, the potential role of the IL-31-IL31RA axis in pulmonary inflammation and fibrosis has remained largely unknown. To determine the role of IL-31RA deficiency in pulmonary fibrosis, wildtype, and IL-31RA knockout mice were treated with bleomycin and measured changes in collagen deposition and lung function. Notably, the loss of IL-31 signaling attenuated collagen deposition and lung function decline during bleomycin-induced pulmonary fibrosis. The total lung transcriptome analysis showed a significant reduction in fibrosis-associated gene transcripts including extracellular matrix and epithelial cell-associated gene networks. Furthermore, the lungs of human IPF showed an elevated expression of IL-31 when compared to healthy subjects. In support, the percentage of IL-31 producing CD4⁺ T cells was greater in the lungs and PBMCs from IPF patients compared to healthy controls. Our findings suggest a pathogenic role for IL-31/IL-31RA signaling during bleomycin-induced pulmonary fibrosis. Thus, therapeutic targeting the IL-31-IL-31RA axis may prevent collagen deposition, improve lung function, and have therapeutic potential in pulmonary fibrosis.

• bleomycin IL-31 regulation of pulmonary fibrosis
• idiopathic pulmonary fibrosis
• interleukin 31
• interleukin 31 receptor alpha
• lung

Chronic hepatitis B virus (HBV) infection is a risk factor for liver cirrhosis (LC) and hepatocellular carcinoma (HCC), however, little is known about the mechanisms involved in the progression of HBV-related diseases. It has been well acknowledged that host immune response was closely related to the clinical outcomes of patients with HBV infection. As the factors closely related to the immunomodulatory process, cytokines are crucial in the cell-cell communication and the host responses to HBV infection. Recently, a newly discovered cytokine, designated as interleukin-35 (IL-35), has been proved to be essential for the progression of chronic HBV infection, the development of cirrhosis, the transformation of cirrhosis to HCC, and the metastasis of HCC. Specifically, it showed various biological activities such as inhibiting the HBV-specific cytotoxic T lymphocyte (CTL) proliferation and cytotoxicity, deactivating the immature effector T-cells (Teffs), as well as delaying the proliferation of dendritic cells. It regulated the immune responses by acting as a “brake” on the activation of Teffs, which subsequently played important roles in the pathogenesis of various inflammatory diseases and malignancies. In this review, we focused on the most recent data on the relationship between IL-35 and chronic HBV infection, LC and HCC.

• chronic hepatitis B
• cytotoxic T lymphocytes
• immunopathology
• induced regulatory T-cells
• interleukin-35

In recent years, the published literature has suggested the key involvement of the cytokine interleukin-31 (IL-31) in the symptomatology of pruritus, and both IL-31 and its receptor have become potential therapeutic targets for a range of pruritic diseases. Elevated levels of IL-31 or its receptor have been reported in the tissue or serum of patients with pruritic skin diseases, such as atopic dermatitis, prurigo nodularis, and psoriasis. Pruritus places a heavy burden on patients, and can have a negative impact on daily life, sleep, and mental health. Since current anti-pruritic treatments are often ineffective, affected patients are in urgent need of new therapies. As a result, drug development targeting the IL-31 pathway is evolving rapidly. To date, only nemolizumab, a humanized monoclonal antibody targeting the IL-31 receptor, has successfully completed late-stage clinical studies. This article will highlight our current clinical understanding of the role of IL-31 in pruritic disease, and explore recent progress in drug development as well as the anticipated future advances in this field.

• anti-IL-31
• anti-IL-31RA
• interleukin-31
• interleukin-31 receptor
• itch
• nemolizumab
• pruritus

It is known that liver diseases have several characteristics of massive lipid accumulation and lipid metabolic disorder, and are divided into liver inflammation, liver fibrosis, liver cirrhosis (LC), and hepatocellular carcinoma (HCC) in patients. Interleukin (IL)-35, a new-discovered cytokine, can protect the liver from the environmental attack by increasing the ratio of Tregs (T regulatory cells) which can increase the anti-inflammatory cytokines and inhibit the proliferation of immune cellular. Interestingly, two opposite mechanisms (pro-inflammatory and anti-inflammatory) have connection with the ultimate formation of liver diseases, which suggest that IL-35 may play crucial function in the process of liver diseases through immunosuppressive regulation. Besides, some obvious advantages also imply that IL-35 can be considered as a new therapeutic target to control the progression of liver diseases, while its mechanism of function still needs further research.

• Interleukin-35
• cellular proliferation
• hepatocellular carcinoma
• lipid accumulation
• liver diseases

• Diagnostic performance
• interleukin-31
• primary biliary cholangitis

• Helicobacter hepaticus
• IL-33
• Inflammation
• Liver fibrosis
• ST2

• Fibrosis
• Hepatitis B virus
• Hepatitis C virus
• Human immunodeficiency virus
• Stiffness
• Treatment

• Antiviral Agents/therapeutic use
• Coinfection/drug therapy
• Coinfection/epidemiology
• Coinfection/pathology
• Coinfection/virology
• Comorbidity
• Disease Progression
• Drug Therapy, Combination
• HIV/immunology
• HIV Infections/drug therapy
• HIV Infections/epidemiology
• HIV Infections/pathology
• HIV Infections/virology
• Hepacivirus/immunology
• Hepatitis B/drug therapy
• Hepatitis B/epidemiology
• Hepatitis B/pathology
• Hepatitis B/virology
• Hepatitis B virus/immunology
• Hepatitis C/drug therapy
• Hepatitis C/epidemiology
• Hepatitis C/pathology
• Hepatitis C/virology
• Humans
• Liver/pathology
• Liver/virology

• K01 AA026864 NIAAA NIH HHS
• R24 OD018546 NIH HHS

• ECM
• OSM
• fibrosis
• inflammation
• vascular injury

• CXCL10
• Interleukin-9
• Liver fibrosis
• Raf/MEK/ERK

• Adult
• Aged
• Aged, 80 and over
• Alanine Transaminase/blood
• CD4 Antigens/analysis
• DNA, Viral/blood
• Disease Progression
• Female
• Flow Cytometry
• Hepatitis B virus/isolation & purification
• Hepatitis B, Chronic/pathology
• Humans
• Interleukins/analysis
• Lymphocyte Count
• Male
• Middle Aged
• Programmed Cell Death 1 Receptor/analysis
• Receptors, CXCR5/analysis
• T-Lymphocytes, Regulatory/chemistry
• T-Lymphocytes, Regulatory/immunology
• Young Adult

The study assessed the correlation between cortisol (COR) levels and concurrent infection for the patients with hepatitis B cirrhosis for corresponding countermeasure analysis. In total, 86 patients with hepatitis B cirrhosis (non-infection group) and 32 patients with hepatitis B cirrhosis complicated with infection (infection group) who were diagnosed and treated in the Beijing YouAn Hospital from March 2014 to March 2017 were selected. The fasting venous blood of all the patients was drawn to detect COR, cortisol binding globulin (CBG), blood routine indexes, C-reactive protein (CRP), procalcitonin (PCT), endotoxin and other indicators. The relative expression of CBG mRNA was detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR). The differences and correlation of COR levels between the infection and non-infection groups were compared and analyzed. The concentrations of COR and CBG were decreased with the increase of Child-Pugh grade, and the difference was statistically significant (P<0.05). COR, CBG and free cortisol (FC) concentrations with the same Child-Pugh grade in the non-infection group were higher than those in the infection group (P<0.05). COR, CBG and FC concentrations of abdominal infection complicated with sepsis or abdominal infection complicated with pulmonary infection were lower than those of simple abdominal infection (P<0.05). The relative expression of CBG mRNA was detected by RT-qPCR, which also showed that: for Child-Pugh grade, grade A > grade B > grade C (P<0.05), non-infection group > infection group (P<0.05), abdominal infection + sepsis group and abdominal infection + pulmonary infection group were lower than the simple abdominal infection group (P<0.05). The values of white blood cells (WBC), neutrophils, CRP, PCT and endotoxin in the infection group were higher than those in the non-infection group, and the differences were statistically significant (P<0.05). COR, CGB and FC were negatively correlated with inflammatory indexes such as WBC, neutrophils, CRP, PCT and endotoxin. The r value of COR and FC in the non-infection group was 0.678, while that of OR and FC in the infection group was 0.787. COR was positively correlated with FC before and after infection. The results of the study show that the cortisol levels of patients with hepatitis B cirrhosis are significantly correlated with whether infected or not, levels of disease condition and infection types, and can be used as sensitive indicators of hepatitis B cirrhosis infection.

• concurrent infection
• correlation
• cortisol
• cortisol binding globulin
• hepatitis B cirrhosis

• HBx
• HCC
• PPM1a
• TGF-β
• tumorigenenesis

• Hepatitis B
• Liver cirrhosis
• Liver failure
• Proinflammatory cytokines
• Resistin

• Bacterial translocation
• HIV
• Liver fibrosis
• Mitochondrial toxicity

• K24 AI096925 NIAID NIH HHS

T helper 9 (Th9) cells, a recently recognized Th cell subset, are involved in autoimmune diseases. We aimed to investigate the role of Th9/interleukin-9 (IL-9) in the pathogenesis of hepatic fibrosis. Th9 and Th17 cells were quantified in chronic hepatitis B (CHB) patients with hepatic fibrosis, HBV-associated liver cirrhosis (LC) patients and healthy controls (HC). The percentages of Th9 and Th17 cells, concentrations of IL-9 and IL-17, as well as expression of IL-17, TNF-α, IL-6, IL-4, IL-21, TGF-β1 and IFN-γ were significantly increased in plasma of CHB and LC patients compared with those in HC. Splenic Th9 and Th17 cells, plasma concentrations and liver expression of IL-9 and IL-17A were significantly elevated in mice with hepatic fibrosis compared with controls. Neutralization of IL-9 in mice ameliorated hepatic fibrosis, attenuated the activation of hepatic stellate cells, reduced frequencies of Th9, Th17 and Th1 cells in spleen, and suppressed expression of IL-9, IL-17A, IFN-γ, TGF-β1, IL-6, IL-4 and TNF-α in plasma and liver respectively. Our data suggest a deleterious role of Th9/IL-9 in increasing hepatic fibrosis and exacerbating disease endpoints, indicating that Th9/IL9 based immunotherapy may be a promising approach for treating hepatic fibrosis.