Anti-inflammatory activity of IL-37 in asthmatic children: Correlation with inflammatory cytokines TNF-α, IL-β, IL-6 and IL-17A

• Published in: Immunobiology (1979) 2016-02, Vol.221 (2), p.182-187
• Main Authors: Charrad, Rihab, Berraïes, Anissa, Hamdi, Besma, Ammar, Jamel, Hamzaoui, Kamel, Hamzaoui, Agnes
• Format: Article
• Language: English
• Subjects: Adolescent; Advanced Basic Science; Allergy and Immunology; Asthma; Asthma - genetics; Asthma - immunology; Asthma - pathology; Case-Control Studies; Child; Child, Preschool; Children; Female; Forced Expiratory Volume - immunology; Gene Expression Regulation; Humans; IL-17; IL-1β; IL-6; Interleukin-1 - genetics; Interleukin-1 - immunology; Interleukin-1 - pharmacology; Interleukin-17 - antagonists & inhibitors; Interleukin-17 - genetics; Interleukin-17 - immunology; Interleukin-1beta - antagonists & inhibitors; Interleukin-1beta - genetics; Interleukin-1beta - immunology; Interleukin-37; Interleukin-6 - antagonists & inhibitors; Interleukin-6 - genetics; Interleukin-6 - immunology; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - immunology; Leukocytes, Mononuclear - pathology; Lipopolysaccharides - pharmacology; Male; Primary Cell Culture; Signal Transduction; Sputum - chemistry; TNF-α; Tumor Necrosis Factor-alpha - antagonists & inhibitors; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - immunology
• ISSN: 0171-2985; 1878-3279
• DOI: 10.1016/j.imbio.2015.09.009

Abstract Background The aim of this study was to assess interleukin (IL)-37 production in asthmatic children in serum and induced sputum and to look to the impact of IL-37 on pro-inflammatory cytokines production (TNF-α, IL-6, IL-1β and IL-17). Methods Forty children with well-controlled asthma (20 moderate and 20 mild asthmatics) were studied. IL-37 was measured by ELISA in serum and induced sputum (IS) samples, and compared with 22 age- and sex-matched healthy controls. Real-time quantitative PCR was used to determine IL-37 mRNA expression in induced sputum cells. Induced sputum mononuclear cells from 10 moderate asthmatics and 10 healthy controls were stimulated either with lipopolysaccharides (LPS) or LPS plus recombinant IL-37 (rIL-37) comparing pro-inflammatory cytokines production. TNF-α, IL-1β, IL-6 and IL-17 were measured by RT-PCR and ELISA. Findings The expression of IL-37 mRNA in asthmatic patients was significantly lower than that observed in healthy controls ( P = 0.0001). IL37 mRNA expression depended on asthma severity. Serum and IS IL-37 levels were significantly lower in asthma patients compared to healthy controls. LPS-stimulated sputum cells from asthma patients produced higher levels of IL-1β, IL-6, and TNF-α than those from HC. Adding rIL-37 suppressed TNF-α, IL-1β and IL-6 production in IS cells. In the same way, stimulating IS CD4+ T cells in the presence of rIL-37 inhibited IL-17 production both in asthma patients and HC. IL-37 effect on IL-17 was more pronounced in patients than controls. Interpretation The decrease in IL-37 level observed in IS was found to correlate with disease severity. The increased pro-inflammatory cytokines production from asthma IS cells was abrogated by the addition of rIL-37. IL-37 could be an important cytokine in the control of asthma by suppressing the production of inflammatory cytokines.