Uncoupling of Airway Inflammation and Bronchial Hyperreactivity

Abstract

We produced transgenic mice which overexpress human IL6 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 cmH2O/ml per s at 9 wk of age, P = NS and 0.45±0.07 vs 0.43±0.09 cmH2O/ml per s at 17 wk of age, P = NS). Transgenic mice, however, required a significantly higher log dose ofmethacholine 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 s 0.01). We conclude that the expression ofhuman 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-6induced 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