IL-11 selectively inhibits aeroallergen-induced pulmonary eosinophilia and Th2 cytokine production.
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-gamma 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.
Wang
J
J
Section of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
Homer
R J
RJ
Hong
L
L
Cohn
L
L
Lee
C G
CG
Jung
S
S
Elias
J A
JA
D000280:Administration, Inhalation; D000336:Aerosols; D000485:Allergens / Q000008:administration & dosage* / Q000276:immunology*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis* / Q000502:physiology; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D007114:Immunization; D017370:Interleukin-11 / Q000008:administration & dosage* / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D009077:Mucins / Q000096:biosynthesis / Q000235:genetics; D009093:Mucus / Q000276:immunology / Q000378:metabolism; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D011657:Pulmonary Eosinophilia / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D011994:Recombinant Proteins / Q000008:administration & dosage; D020545:Respiratory Mucosa / Q000276:immunology / Q000378:metabolism; D013045:Species Specificity; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism*; D014422:Turkeys; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis
D000336:Aerosols; D000485:Allergens; D016207:Cytokines; D017370:Interleukin-11; D009077:Mucins; D011994:Recombinant Proteins; D019010:Vascular Cell Adhesion Molecule-1; D010047:Ovalbumin