AIRWAY EPITHELIAL-CELL EXPRESSION OF INTERLEUKIN-6 IN TRANSGENIC MICE - UNCOUPLING OF AIRWAY INFLAMMATION AND BRONCHIAL HYPERREACTIVITY

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 cmH(2)O/ml per s at 9 wk of age, P = NS and 0.45+/-0.07 vs 0.43+/-0.09 cmH(2)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 less than or equal to 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.