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Background: The interleukin (IL)-36 cytokines include IL-36α, IL-36β, IL-36γ, and IL-36Ra. Little was known about their roles in type 2 diabetes mellitus (T2DM)., Methods: The study included 40 T2DM patients and 42 healthy control subjects. The anthropometric and biochemical measurements were performed using automatic biochemical analyzer, high-performance liquid chromatography, and electrochemiluminescence immunoassay. Circulating IL-36α, IL-36γ, IL-36Ra, and IL-17 levels were determined by enzyme-linked immunosorbent assay., Results: Serum IL-36α, IL-36γ, and IL-17 levels in T2DM patients were significantly higher than those in controls, whereas serum IL-36Ra levels in T2DM patients were lower. Correlation analysis showed that serum IL-36α was positively correlated with high sensitivity C-reactive protein. Serum IL-36α was negatively correlated with IL-36Ra. Serum IL-17 was negatively correlated with low-density lipoprotein cholesterol., Conclusions: This study demonstrated that T2DM patients displayed increased IL-36α and IL-36γ expression and decreased IL-36Ra expression. Moreover, the inflammatory cytokine levels were directly proportional to the inflammation and blood lipid levels. Our results suggest that IL-36 cytokines may be a new target for the diagnosis or treatment of T2DM., (© 2020 The Authors. Journal of Clinical Laboratory Analysis Published by Wiley Periodicals LLC.)

Obesity is associated with a chronic inflammatory response. Interleukin (IL)-38 is a poorly characterized cytokine of the IL-1 family with anti-inflammatory activity. The role of IL-38 in obesity-induced inflammation and insulin resistance remains unknown. In this study, we investigated the effects of IL-38 expression by hydrodynamic-based gene delivery on high-fat diet-induced obesity in mice. Transfer of plasmid DNA encoding IL-38 reduced weight gain, liver fat content, adipose tissue weight, and obesity-induced insulin resistance compared with administration of a control plasmid. Moreover, IL-38 gene delivery inhibited the production of inflammatory mediators including IL-1β, IL-6, and monocyte chemotactic protein-1. These results suggest that IL-38 is a potential new target for the treatment of obesity., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Interleukin-1 family 7 (IL-1F7) is a novel member of IL-1F cytokines. IL-1F7 is more commonly known as IL-37. IL-37 can join the α-subunit of the IL-18 receptor, or IL-18 binding protein (IL-18BP), and binding of these proteins can enhance the IL-18 suppression. IL-37 also translocates to the cell nucleus and affects gene transcription. IL-37 inhibits the phosphorylation of p38 mitogen-activated protein kinases. Almost all reports showed that IL-37 has remarkable anti-inflammatory activity. IL-37 plays an important role in a variety of inflammatory and autoimmune diseases, as well. Recently, studies demonstrated that the expression of IL-37 is abnormal in many diseases such as inflammatory bowel diseases, inflammatory respiratory diseases, atherosclerosis, hepatitis, obesity, contact hypersensitivity, Graves' disease, rheumatoid arthritis, ankylosing spondylitis, systemic lupus erythematosus, multiple sclerosis, psoriasis, and Behcet's disease. Here, we will review the biological characteristics of IL-37 and its key roles in various inflammatory and autoimmune diseases.

Objective and Design: Asthma is thought to result from the generation of T helper type 2 (Th2) responses, leading to bronchial inflammation. Interleukin (IL)-35 is a recently described member of IL-12 cytokine family that plays a critical role in influencing Th cell differentiation and inflammatory processes. The aim of this study was to examine the effect of adenovirus expressing IL-35 (AdIL-35) on allergic airway hyperresponsiveness (AHR) and inflammation in a mouse model of asthma., Methods: BALB/c mice were subjected to an established model of allergic airway disease. AdIL-35 was administered intranasally and the effect of IL-35 on Th2 responses, pulmonary inflammation, goblet cell metaplasia, and AHR were assessed., Results: Transfer of AdIL-35 significantly reduced the severity of AHR and numbers of inflammatory cells and levels of IL-4, IL-5, IL-13, and IL-17 in bronchoalveolar lavage fluid, compared with administration of a control virus. Moreover, AdIL-35 elevated the numbers of CD4+CD25+Foxp3+ regulatory T cells in the lungs. Histological analysis showed that AdIL-35 inhibited allergic lung tissue inflammation and mucus hypersecretion., Conclusion: These results demonstrate that adenovirus-mediated delivery of interleukin-35 gene can mitigate allergic airway inflammation in experimental asthma and suggest that IL-35 may offer a novel therapeutic approach to treat allergic asthma.

Interleukin- (IL-) 38 is a recently discovered cytokine and is the tenth member of the IL-1 cytokine family. IL-38 shares structural features with IL-1 receptor antagonist (IL-1Ra) and IL-36Ra. IL-36R is the specific receptor of IL-38, a partial receptor antagonist of IL-36. IL-38 inhibits the production of T-cell cytokines IL-17 and IL-22. IL-38 also inhibits the production of IL-8 induced by IL-36γ, thus inhibiting inflammatory responses. IL-38-related cytokines, including IL-1Ra and IL-36Ra, are involved in the regulation of inflammation and immune responses. The study of IL-38 and IL-38-related cytokines might provide new insights for developing anti-inflammatory treatments in the near future.

Interleukin (IL)-39 is a novel member of IL-12 family and has been reported to play a pro-inflammatory role in lupus-like mice, but its function in concanavalin A (ConA)-induced liver injury is currently unclear. In this study, we investigated the effects of IL-39 expression in a mouse model of ConA induced-hepatitis. We first showed that delivery of plasmid DNA encoding mouse IL-39 using the hydrodynamic tail vein injection method increased IL-39 mRNA and protein levels in the liver. We then administrated mice with IL-39 plasmid before ConA injection and measured serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, inflammatory infiltration, and hepatocyte necrosis in the liver. Additionally, we further explored the potential mechanism of IL-39 in ConA-induced liver injury by measuring several inflammatory mediators. We found that ectopic IL-39 expression promoted the ConA-induced increase in serum ALT and AST levels, inflammatory infiltration, and hepatocyte necrosis in the liver. We also observed that IL-39 plasmid administration significantly increased serum and liver interferon-γ, tumor necrosis factor-α, and IL-17A levels, but did not affect serum and liver IL-10 levels in ConA-induced hepatitis. Our results suggest that IL-39 can exacerbate ConA-induced hepatitis and may be a therapeutic target in inflammatory liver disease. [ABSTRACT FROM AUTHOR]

Abstract: IL-33 is a recently described member of the IL-1 family that has been reported to have a pathogenic role in several inflammatory diseases. In this study, we evaluated the role of IL-33 in a murine model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). We showed that the expression of IL-33 and its receptor, ST2, was markedly elevated in the spinal cord of mice during myelin oligodendrocyte glycoprotein (MOG)35–55 peptide-induced EAE. Administration of a blocking anti-IL-33 antibody in mice of EAE during the induction phase significantly inhibited the onset and severity of EAE and reduced MOG35–55-induced IFN-γ and IL-17 production. In contrast, treatment with recombinant IL-33 worsened the disease course of EAE in association with increased induction of both IFN-γ and IL-17. Furthermore, anti-IL-33 treatment caused a remarkable decrease in expression of IL-17, IFN-γ, T-bet and RORγt, and an upregulation of IL-10 and TGF-β in the spinal cord of EAE mice. These results demonstrate that endogenous IL-33 plays a pivotal role in the pathogenesis of EAE and indicate that blockade of IL-33 has a significant protective effect against EAE. [Copyright &y& Elsevier]

It has been shown that the expression of ST2, a receptor of interleukin (IL)-33, is elevated in the lungs of idiopathic pulmonary fibrosis patients and bleomycin-induced mouse models, however its contribution to the development of pulmonary fibrosis has yet to be tested. In the present study, we treated mice by intranasal instillation of lentivirus expressing soluble ST2 and evaluated lung inflammation and fibrosis in the bleomycin-induced pulmonary fibrosis mouse model. We found that ST2 lentivirus treatment significantly improved survival rate and reduced weight loss compared with controls treated with empty lentivirus. Furthermore, ST2 treatment profoundly attenuated the pulmonary inflammatory cell infiltration and fibrotic changes. Finally, ST2 treatment markedly lowered the levels of IL-4, IL-6, IL-13, IL-33, monocyte chemoattractant protein-1, and transforming growth factor-β1, whereas it increased the levels of interferon-γ in bronchoalveolar lavage fluid. The results indicate that ST2 might prevent bleomycin-induced pulmonary fibrosis possibly through downregulating proinflammatory and profibrotic mediators. This study suggests that lentivirus expressing soluble ST2 might represent an effective therapeutic approach in the treatment of pulmonary fibrotic diseases. [ABSTRACT FROM AUTHOR]

Abstract: Background: Asthma is thought to result from the generation of T helper type 2 (Th2) responses, leading to bronchial inflammation. IFN-λ1 (also known as IL-29) is a recently described member of the IFN-λ family and has been shown to decrease production of Th2 cytokines in vitro. However, the role and mechanism of IFN-λ1 in asthma remain unknown. Objectives: The aim of this study was to clarify the importance of IFN-λ1 in allergen-induced airway hyperresponsiveness (AHR) and inflammation. Methods: We used a murine model for ovalbumin (OVA)-induced asthma to examine the effect of intranasal delivery of recombinant adenovirus expressing human IFN-λ1 (Ad-hIFN-λ1) on AHR and allergic airway inflammation. Results: Intranasal instillation of Ad-hIFN-λ1 before airway antigen challenge in OVA-immunized mice significantly decreased the severity of AHR and numbers of eosinophils and levels of IL-4, IL-5, and IL-13, but not IL-10 and IFN-γ; both in vivo, in the bronchoalveolar lavage fluid and in vitro, following stimulation of lymphocytes from spleens with OVA, compared with administration of a control virus (Ad-mock). Furthermore, Ad-hIFN-λ1 treatment inhibited serum IgE secretion and increased numbers of splenic CD4+CD25+FOXP3 + Treg cells. Histological studies showed that Ad-hIFN-λ1 attenuated OVA-induced lung tissue eosinophilia. Conclusions: These results demonstrate that delivery of the Ad-hIFN-λ1 can mitigate allergic airway inflammation in experimental asthma. The potent immunoregulatory action of IFN-λ1 may offer a novel therapeutic approach to treat allergic asthma. [Copyright &y& Elsevier]