Inhibition of interleukin-1beta reduces mouse lung inflammation induced by exposure to cigarette smoke.

We examined nuclear factor kappaB activation, release of inflammatory mediators and cellular infiltration in acute cigarette smoke inflammation models. One hour after exposure to one puff of cigarette smoke, alveolar macrophages from bronchoalveolar lavage (BAL) fluid of C57BL/6J mice showed an increased activity of nuclear factor kappaB-DNA binding but similar numbers as compared to that of BAL fluid from mice exposed to ambient air. Exposure to 1 cigarette/day for 1, 4 or 7 days led to an increase in interleukin-1beta and monocyte chemoattractant protein-1 levels and to a progressive influx of nuclear factor kappaB-activated alveolar macrophages into the BAL fluid and lung tissue. Exposure to 2 cigarettes/day for 7 days led to a significant increase in interleukin-1beta levels accompanied by a massive alveolar macrophage influx into the BAL fluid. Tumor necrosis factor-alpha levels and subsequent neutrophil influx were only detected after exposure to 4 or 8 cigarettes/day for 7 days. Treatment of mice with an antibody anti-interleukin-1beta during cigarette smoke exposure for 7 days significantly reduced both interleukin-1beta levels and alveolar macrophage influx. These data show that a single exposure to cigarette smoke rapidly activates alveolar macrophages, inducing the production of interleukin-1beta, which may play an important role in triggering chronic cigarette smoke-mediated lung inflammation.