Endogenous and exogenous IL-6 inhibit aeroallergen-induced Th2 inflammation

Chronic Th2-dominated inflammation and exaggerated IL-6 production are char acteristic features of the asthmatic airway. To understand the processes th at are responsible for the chronicity of this response and the role(s) of I L-6 in the regulation of airway Th2 inflammation, we compared the responses induced by OVA in sensitized wild-type mice, IL-6 deficient (-/-) mice, an d 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 exaggerat ed inflammation and eosinophilia, increased levels of IL-4, IL-5, and IL-13 protein and mRNA, exaggerated levels of eotaxin, JE/monocyte chemoattracta nt protein-1, macrophage inflammatory protein-1 alpha and -2, and mRNA, inc reased bronchoalveolar lavage (BAL) TGF-beta(1), and exaggerated airway res ponses to aerosolized methacholine. In contrast, CC10-IL-6 mice, on both C5 7BL/6 and BALB/c backgrounds, manifest diminished inflammation and eosinoph ilia, decreased levels of IL-4, IL-5, and IL-13 protein and mRNA, and decre ased levels of bronchoalveolar lavage TGF-beta(1), 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 wer e not associated with significant decreases or increases in the levels of I FN-gamma, respectively. These studies demonstrate that endogenous and exoge nous IL-6 inhibit aeroallergen-induced Th2 inflammation and that this inhib ition is not mediated by regulatory effects of IFN-gamma. IL-6 may be an im portant anti-inflammatory, counterregulatory, and healing cytokine in the a irway.