Rihab Charrad1, Anissa Berraïes2, Besma Hamdi2, Jamel Ammar2, Kamel Hamzaoui3, Agnes Hamzaoui2. 1. Unit Research 12SP15 "Homeostasis and Cell Dysfunction", Abderrahman Mami Hospital, Ariana,Tunisia; El Manar Tunis University, Faculty of Medicine of Tunis, Department of Basic Sciences, Tunis, Tunisia. 2. Unit Research 12SP15 "Homeostasis and Cell Dysfunction", Abderrahman Mami Hospital, Ariana,Tunisia; El Manar Tunis University, Faculty of Medicine of Tunis, Department of Basic Sciences, Tunis, Tunisia; Division of Pulmonology, Department of Paediatric Respiratory Diseases, Abderrahman Mami Hospital, Ariana, Tunisia. 3. Unit Research 12SP15 "Homeostasis and Cell Dysfunction", Abderrahman Mami Hospital, Ariana,Tunisia; El Manar Tunis University, Faculty of Medicine of Tunis, Department of Basic Sciences, Tunis, Tunisia. Electronic address: kamel.hamzaoui@gmail.com.
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.
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 asthmapatients compared to healthy controls. LPS-stimulated sputum cells from asthmapatients 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 asthmapatients 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.
Authors: Elan Z Eisenmesser; Adrian Gottschlich; Jasmina S Redzic; Natasia Paukovich; Jay C Nix; Tania Azam; Lingdi Zhang; Rui Zhao; Jeffrey S Kieft; Erlinda The; Xianzhong Meng; Charles A Dinarello Journal: Proc Natl Acad Sci U S A Date: 2019-02-28 Impact factor: 11.205