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*
Section of Pulmonary and Critical Care Medicine, Department of Internal Medicine,
Department of Pathology, and
Section of Rheumatology, Yale University School of Medicine, New Haven, CT 06520; Pathology and Laboratory Medicine Service, Veterans Affairs-Connecticut Healthcare System, West Haven, CT 06516
IL-11 is a pleiotropic cytokine that induces tissue remodeling with
subepithelial fibrosis when expressed in the airway. Its effects on the
Th2-dominated airway inflammation that is characteristic of asthma,
however, are poorly understood. To characterize the effects of IL-11 on
Th2 tissue inflammation, we compared the inflammatory responses
elicited by OVA in sensitized mice 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-specific IgE after sensitization. OVA challenge of sensitized
transgene- mice caused airway and parenchymal eosinophilic
inflammation, Th2 cell accumulation, and mucus
hypersecretion with mucus metaplasia. Exaggerated levels of
immunoreactive endothelial cell VCAM-1, mucin (Muc) 5ac gene expression
and bronchoalveolar lavage and lung IL-4, IL-5, and IL-13 protein and
mRNA were also noted. In contrast, OVA challenge in CC10-IL-11 animals
elicited impressively lower levels of tissue and bronchoalveolar lavage
inflammation, eosinophilia, 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 comparable decrease in mucus
hypersecretion, Muc 5ac gene expression, or the level of expression of
RANTES, monocyte chemoattractant protein-2, or monocyte chemoattractant
protein-3. In addition, IL-11 did not augment IFN-
production
demonstrating that the inhibitory effects of IL-11 were not due to a
shift toward Th1 inflammation. These studies demonstrate that IL-11
selectively inhibits Ag-induced eosinophilia, Th2 inflammation, and
VCAM-1 gene expression in pulmonary tissues.
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