IL-11 selectively inhibits aeroallergen-induced pulmonary eosinophilia andTh2 cytokine production

IL-11 is a pleiotropic cytokine that induces tissue remodeling with subepit helial fibrosis when expressed in the airway. Its effects on the Th2-domina ted airway inflammation that is characteristic of asthma, however, are poor ly understood. To characterize the effects of IL-11 on Th2 tissue inflammat ion, we compared the inflammatory responses elicited by OVA in sensitized m ice in which IL-11 is overexpressed in a lung-specific fashion (CC10-IL-11) with that in transgene(-) wild-type littermate controls. Transgene(-) and CC10-IL-11 transgene(+) mice had comparable levels of circulating Ag-specif ic IgE after sensitization. OVA challenge of sensitized transgene- mice cau sed airway and parenchymal eosinophilic inflammation, Th2 cell accumulation , and mucus hypersecretion with mucus metaplasia, Exaggerated levels of imm unoreactive endothelial cell VCAM-1, mucin (Muc) 5ac gene expression and br onchoalveolar lavage and lung IL-4, IL-5, and IL-13 protein and mRNA were a lso noted. In contrast, OVA challenge in CC10-IL-11 animals elicited impres sively lower levels of tissue and bronchoalveolar lavage inflammation, eosi nophilia, and Th2 cell accumulation, and significantly lower levels of VCAM -1 and IL-4, IL-5, and IL-13 mRNA and protein, IL-11 did not cause a compar able decrease in mucus hypersecretion, Muc 5ac gene expression, or the leve l of expression of RANTES, monocyte chemoattractant protein-2, or monocyte chemoattractant protein-3. In addition, IL-11 did not augment IFN-gamma pro duction demonstrating that the inhibitory effects of IL-11 were not due to a shift toward Th1 inflammation. These studies demonstrate that IL-11 selec tively inhibits Ag-induced eosinophilia, Th2 inflammation, and VCAM-1 gene expression in pulmonary tissues.