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 infiltra te adjacent to large and mid-sized airways. Immunohistochemistry revea ls 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 cm H(2)O/ml per s at 17 wk of age, P = NS). Transgenic mice, however, req uired a significantly higher log dose of methacholine to produce a 100 % increase in respiratory system resistance as compared with nontransg enic littermates (1.34+/-0.24 vs 0.34+/-0.05 mg/ml, P less than or equ al to 0.01). We conclude that the expression of human IL-6 in the airw ays of transgenic mice results in a CD4(+), MHC class II+, B220(+) lym phocytic infiltrate surrounding large and mid-sized airways that does not alter basal respiratory resistance, but does diminish airway react ivity to methacholine. These findings demonstrate an uncoupling of IL- 6-induced airway lymphocytic inflammation and airway hyperresponsivene ss and suggest that some forms of airway inflammation may serve to res tore altered airway physiology.