Interleukin-1 beta inhibits airway smooth muscle contraction via epithelium-dependent mechanism.

To determine whether the cytokine interleukin (IL)-1 beta directly affects airway smooth muscle functions and, if so, what the mechanism of action is, we studied canine isolated bronchial segments under isometric conditions in vitro. Incubation of tissues with human recombinant IL-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 52 +/- 8% (mean +/- SD, p < 0.001) observed with 10 ng/ml IL-1 beta. Intracellular levels of cyclic AMP and cyclic GMP were not significantly altered by IL-1 beta. The IL-1 beta-induced inhibition of the contractile responses was not affected by pretreatment of tissues with indomethacin or propranolol, but it was greatly attenuated by mechanical removal of epithelium. These results suggest that IL-1 beta may play a protective role against bronchoconstrictor responses via epithelium-dependent mechanism such as the release of epithelium-derived relaxing factor.