Pulmonary expression of interleukin-13 causes inflammation, mucus hypersecretion, subepithelial fibrosis, physiologic abnormalities, and eotaxin production

Interleukin (IL)-13 is a pleiotropic cytokine produced in large quantities by activated CD4(+) Th2 lymphocytes. To define further its potential in viv o effector functions, the Clara cell 10-kDa protein promoter was used to ex press IL-13 selectively in the lung, and the phenotype of the resulting tra nsgenic mice was characterized. In contrast to transgene-negative littermat es, the lungs of transgene-positive mice contained an inflammatory response around small and large airways and in the surrounding parenchyma. It was m ononuclear in nature and contained significant numbers of eosinophils and e nlarged and occasionally multinucleated macrophages. Airway epithelial cell hypertrophy, mucus cell metaplasia, the hyperproduction of neutral and aci dic mucus, the deposition of Charcot-Leyden-like crystals, and subepithelia l airway fibrosis were also prominently noted. Eotaxin protein and mRNA wer e also present in large quantities in the lungs of the transgene-positive, but not the transgene-negative, mice. IL-4, IL-5, granulocyte-macrophage co lony-stimulating factor, and monocyte chemoattractant protein-5 were not si milarly detected. Physiological evaluations revealed significant increases in base-line airways resistance and airways hyperresponsiveness (AHR) to me thacholine in transgene-positive animals. Thus, the targeted pulmonary expr ession of IL-13 causes a mononuclear and eosinophilic inflammatory response , mucus cell metaplasia, the deposition of Charcot-Leyden-like crystals, ai rway fibrosis, eotaxin production, airways obstruction, and nonspecific AHR . IL-13 may play an important role in the pathogenesis of similar responses in asthma or other Th2-polarized tissue responses.