Am. J. Respir. Crit. Care Med., Vol 149, No. 1, 01 1994, 134-137.
Interleukin-1 beta inhibits airway smooth muscle contraction via epithelium-dependent mechanism
J Tamaoki, I Yamawaki, K Takeyama, A Chiyotani, F Yamauchi and K Konno
First Department of Medicine, Tokyo Women's Medical College, Japan.
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.