Airway Epithelial Cell Expression of Interleukin-6 in Transgenic Mice: Uncoupling of Airway Inflammation and Bronchial Hyperreactivity

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We produced transgenic mice which overexpress human IL-6 in the airway epithelial cells. Transgenic mice develop a mononuclear cell infiltrate adjacent to large and mid-sized airways. Immunohistochemistry reveals these cells to be predominantly CD4+ cells, MHC class II+ cells, and B220+ cells. Transgenic mice and nontransgenic mice had similar baseline respiratory system resistance (0.47 +/-0.06 vs 0.43 +/-0.04 cmH2 O/ml per s at 9 wk of age, P = NS and 0.45 +/-0.07 vs 0.43 +/-0.09 cmH2 O/ml per s at 17 wk of age, P = NS). Transgenic mice, however, required a significantly higher log dose of methacholine to produce a 100% increase in respiratory system resistance as compared with nontransgenic littermates (1.34 +/-0.24 vs 0.34 +/-0.05 mg/ml, P <= 0.01). We conclude that the expression of human IL-6 in the airways of transgenic mice results in a CD4 (+), MHC class II+, B220+ lymphocytic infiltrate surrounding large and mid-sized airways that does not alter basal respiratory resistance, but does diminish airway reactivity to methacholine. These findings demonstrate an uncoupling of IL-6-induced airway lymphocytic inflammation and airway hyperresponsiveness and suggest that some forms of airway inflammation may serve to restore altered airway physiology. (J. Clin. Invest. 1994. 94:2028-2035.) Key words: cytokines. airway physiology. lung biology. methacholine. airway hyperresponsiveness

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