INTERLEUKIN-1-BETA INHIBITS AIRWAY SMOOTH-MUSCLE CONTRACTION VIA EPITHELIUM-DEPENDENT MECHANISM

To determine whether the cytokine interleukin (IL)-1 beta directly aff ects airway smooth muscle functions and, if so, what the mechanism of action is, we studied canine isolated bronchial segments under isometr ic conditions in vitro. Incubation of tissues with human recombinant I L-1 beta (10 ng/ml) for 150 min decreased the contractile responses to acetylcholine, histamine, and KCl. The inhibitory effect of IL-1 beta on the acetylcholine (10(-3) M)-induced contraction was concentration -dependent, the maximal decrease from the baseline contraction being 5 2 +/- 8% (mean +/- SD, p < 0.001) observed with 10 ng/ml IL-1 beta. In tracellular revels of cyclic AMP and cyclic GMP were not significantly altered by IL-1 beta. The IL-1 beta-induced inhibition of the contrac tile responses was not affected by pretreatment of tissues with indome thacin or propranolol, but it was greatly attenuated by mechanical rem oval of epithelium. These results suggest that IL-1 beta may play a pr otective role against bronchoconstrictor responses via epithelium-depe ndent mechanism such as the release of epithelium-derived relaxing fac tor.