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Rheumatoid arthritis (RA) is considered a systemic chronic inflammatory joint disease characterized by chronic synovitis and cartilage and bone destruction. Interleukin-33 (IL-33) is a proinflammatory cytokine which is highly expressed in the synovium of RA patients and the joints of mice with collagen-induced arthritis (CIA) and exacerbates CIA in mice. However, the role of the IL-33-neutralizing antibody in the murine model of CIA remains unclear. In the present study, CIA mice were given intraperitoneally with polyclonal rabbit anti-murine IL-33 antibody (anti-IL-33) or normal rabbit IgG control after the first signs of arthritis. Administration of anti-IL-33 after the onset of disease significantly reduced the severity of CIA and joint damage compared with controls treated with normal rabbit IgG. Anti-IL-33 treatment also significantly decreased the serum levels of interferon- γ (IFN- γ ),IL-6, IL-12, IL-33, and tumor necrosis factor- α (TNF- α ). Moreover, anti-IL-33 treatment significantly downregulated the production of IFN- γ , IL-6, IL-12, IL-33, and TNF- α in ex vivo-stimulated spleen cells. Together, our results indicate that the IL-33-neutralizing antibody may provide a therapeutic strategy for RA by inhibiting the release of proinflammatory cytokines., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Yan Li et al.)

The mechanism by which cigarette smoke ( CS) causes chronic obstructive pulmonary disease ( COPD) is poorly understood. Interleukin-33 ( IL-33) is a pleiotropic cytokine predominantly expressed in lung tissue and can elicit airway inflammation in naive mice. We tested the hypothesis that IL-33 is induced by CS and contributes to CS-mediated airway inflammation in a mouse model of CS-induced COPD. Groups of mice were exposed to CS three times per day for 4 consecutive days. The expression levels of IL-33 and ST2 were markedly enhanced in the lung tissue of mice inhaling CS. Exposure to CS also induced neutrophil and macrophage infiltration and expression of inflammatory cytokines ( IL-1β, tumour necrosis factor-α, IL-17), chemokines (monocyte chemoattractant protein-1) and mucin 5, subtypes A and C in the airways. More importantly, all of these CS-induced pathogenic changes were significantly inhibited by treatment with neutralizing anti- IL-33 antibody delivered intranasally. Hence, our results suggest that IL-33 plays a critical role in CS-mediated airway inflammation and may be a therapeutic target in CS-related diseases, including COPD. [ABSTRACT FROM AUTHOR]

Abstract: Interleukin (IL)-33 is a recently described member of the IL-1 family and has been shown to induce production of T helper type 2 cytokines. In this study, an anti-IL-33 antibody was evaluated against pulmonary inflammation in mice sensitized and challenged with ovalbumin. The anti-IL-33 or a control antibody (150μg/mouse) was given intraperitoneally as five doses before the sensitization and antigen challenge. Treatment with anti-IL-33 significantly reduced serum IgE secretion, the numbers of eosinophils and lymphocytes, and concentrations of IL-4, IL-5, and IL-13 in bronchoalveolar lavage fluid compared with administration of a control antibody. Histological examination of lung tissue demonstrated that anti-IL-33 significantly inhibited allergen-induced lung eosinophilic inflammation and mucus hypersecretion. Our data demonstrate for the first time that anti-IL-33 antibody can prevent the development of asthma in a mouse model and indicate that blockade of IL-33 may be a new therapeutic strategy for allergic asthma. [Copyright &y& Elsevier]

• Serum IL-36γ level was significantly elevated in HT patients. • Serum IL-36γ level was correlated with TPO-Ab titers in HT patients. • IL-36γ may serve as a potential diagnostic biomarker for HT. Hashimoto's thyroiditis (HT) is the predominant cause of primary hypothyroidism. Interleukin (IL)-36γ is a member of the IL-36 family. Recently, IL-36γ was shown to possess proinflammatory properties in autoimmune diseases. However, the role of IL-36γ in HT is insufficiently understood. The purpose of the present study was to investigate the potential relationship between IL-36γ and HT. We included 100 subjects, among whom, 52 had early-stage HT and 48 were healthy controls (HC). The subjects' basic clinical information was obtained through physical examination and clinical histories of signs and symptoms. Thyroid function and measurements of thyroid-stimulating hormone (TSH), free triiodothyronine 3, free triiodothyronine 4 (FT4), thyroid peroxidase antibody (TPO-Ab), and thyroid globulin antibody were measured using a fully automated chemiluminescent immunoassay analyzer. The expression levels of serum IL‐36γ were determined using an enzyme-linked immunosorbent assay. The serum IL-36γ level in the HT group was significantly higher compared with that of the HC group [91.91 (67.52, 130.90) pg/mL vs 62.50 (44.61, 91.53) pg/mL, P < 0.0001]. Correlation analysis showed a negative correlation between serum IL-36γ and TPO-Ab titers in the HT group (r = -0.3507, P = 0.0054). According to receiver operating characteristic curve analysis, the area under the curve (AUC) for IL-36γ was 0.7278 (P < 0.0001), and the AUC for IL-36γ combined with TSH and FT4 was 0.8109 (P < 0.0001). The present study indicates that serum IL-36γ expression is increased in patients with HT and negatively correlates with TPO-Ab. Our findings suggest that IL-36γ may be involved in the development of HT and may therefore serve as a potential new diagnostic biomarker for HT. [ABSTRACT FROM AUTHOR]

• Serum IL-39 levels were significantly higher in patients with RA. • Serum IL-39 levels positively correlated with rheumatoid factor, erythrocyte sedimentation rate, and IgM. • IL-39 may serve as biomarker for the diagnosis of RA. Imbalances in cytokine networks have been shown to be a possible cause of rheumatoid arthritis (RA). The interleukin (IL)-12 family is involved in the pathogenesis of autoimmune diseases including RA, while IL-39 is a newly discovered member of the IL-12 family, although its role in RA remains unclear. The purpose of the present study was to detect the expression of IL-39 in the sera of patients with RA and its relationship with RA activity. We recruited 46 patients with RA and 35 healthy controls at Ningbo Sixth Hospital. Blood samples were collected for biochemical analysis, and disease activity scores of 28 joints based on C-reactive protein were monitored. Serum concentrations of IL-39 were determined using an enzyme-linked immunosorbent assay. The Pearson correlation test was used to analyze the association between serum IL-39 levels and clinical indicators. Serum levels of IL-39 were significantly higher in patients with RA compared with healthy controls (p < 0.0001). IL-39 levels positively correlated with rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), and IgM; RF positively correlated with ESR. Receiver operating characteristic curve analysis showed that IL-39 has diagnostic value for RA (p < 0.0001). The significant increase of IL-39 levels in serum of patients with RA and its positive correlation with clinical indicators suggest that IL-39 may serve as biomarker for the diagnosis of RA. [ABSTRACT FROM AUTHOR]

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]