title: Endogenous and exogenous IL-6 inhibit aeroallergen-induced Th2 inflammation.
abstract: Chronic Th2-dominated inflammation and exaggerated IL-6 production are characteristic features of the asthmatic airway. To understand the processes that are responsible for the chronicity of this response and the role(s) of IL-6 in the regulation of airway Th2 inflammation, we compared the responses induced by OVA in sensitized wild-type mice, IL-6 deficient (-/-) mice, and transgenic mice in which IL-6 was overexpressed in the airway (CC10-IL-6 mice). When compared with wild-type mice, IL-6-/- mice manifest exaggerated inflammation and eosinophilia, increased levels of IL-4, IL-5, and IL-13 protein and mRNA, exaggerated levels of eotaxin, JE/monocyte chemoattractant protein-1, macrophage inflammatory protein-1alpha and -2, and mRNA, increased bronchoalveolar lavage (BAL) TGF-beta1, and exaggerated airway responses to aerosolized methacholine. In contrast, CC10-IL-6 mice, on both C57BL/6 and BALB/c backgrounds, manifest diminished inflammation and eosinophilia, decreased levels of IL-4, IL-5, and IL-13 protein and mRNA, and decreased levels of bronchoalveolar lavage TGF-beta1. IL-6 also decreased the expression of endothelial VCAM-1 and airway responsiveness to methacholine in these animals. These alterations in the IL-6-/- and CC10-IL-6 mice were not associated with significant decreases or increases in the levels of IFN-gamma, respectively. These studies demonstrate that endogenous and exogenous IL-6 inhibit aeroallergen-induced Th2 inflammation and that this inhibition is not mediated by regulatory effects of IFN-gamma. IL-6 may be an important anti-inflammatory, counterregulatory, and healing cytokine in the airway.
authors.affiliation: Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.forename: R J
authors.initials: RJ
authors.lastname: Homer
authors.forename: Q
authors.initials: Q
authors.lastname: Chen
authors.forename: J A
authors.initials: JA
authors.lastname: Elias
mesh_terms: D000281:Administration, Intranasal; D000336:Aerosols; D000485:Allergens / Q000008:administration & dosage* / Q000276:immunology; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000503:physiopathology; D018925:Chemokines / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D005786:Gene Expression Regulation / Q000276:immunology; D007249:Inflammation / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D015850:Interleukin-6 / Q000008:administration & dosage* / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D010993:Plethysmography, Whole Body; D011657:Pulmonary Eosinophilia / Q000235:genetics / Q000276:immunology* / Q000473:pathology* / Q000517:prevention & control; D012333:RNA, Messenger / Q000096:biosynthesis; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis
chemical_list: D000336:Aerosols; D000485:Allergens; D018925:Chemokines; D016207:Cytokines; D015850:Interleukin-6; D012333:RNA, Messenger; D019010:Vascular Cell Adhesion Molecule-1; D010047:Ovalbumin