title: Anti-inflammatory activity of IL-37 in asthmatic children: Correlation with inflammatory cytokines TNF-α, IL-β, IL-6 and IL-17A.
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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.affiliation: 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.
authors.forename: Rihab
authors.initials: R
authors.lastname: Charrad
authors.affiliation: 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.
authors.forename: Anissa
authors.initials: A
authors.lastname: Berraïes
authors.affiliation: 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.
authors.forename: Besma
authors.initials: B
authors.lastname: Hamdi
authors.affiliation: 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.
authors.forename: Jamel
authors.initials: J
authors.lastname: Ammar
authors.affiliation: 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.
authors.forename: Kamel
authors.initials: K
authors.lastname: Hamzaoui
authors.affiliation: 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.
authors.forename: Agnes
authors.initials: A
authors.lastname: Hamzaoui
mesh_terms: D000293:Adolescent; D001249:Asthma / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D005541:Forced Expiratory Volume / Q000276:immunology; D005786:Gene Expression Regulation; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D020381:Interleukin-17 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D061251:Primary Cell Culture; D015398:Signal Transduction; D013183:Sputum / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D000093242:Interleukin-6 Inhibitors
chemical_list: D007375:Interleukin-1; D020381:Interleukin-17; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors; C508717:IL17A protein, human; C508587:IL37 protein, human; C508600:IL6 protein, human
keywords: Asthma; Children; IL-17; IL-1β; IL-6; Interleukin-37; TNF-α