MODULATION OF IL-1-BETA, IL-6, IL-8, TNF-ALPHA, AND TGF-BETA SECRETIONS BY ALVEOLAR MACROPHAGES UNDER NO2 EXPOSURE

Activated alveolar macrophages (AMs) secrete interleukine (IL)-1 beta, IL-6, IL-8, tumor necrosis factor-alpha (TNF-alpha), and transforming growth factor-beta (TGF-beta), whose inflammatory and fibroblast-acti vating characteristics may play a role in the maintenance of pulmonary inflammatory processes and subsequent fibrosis. Human AMs were transf erred to a gas cylinder and exposed to NO2 in concentrations ranging f rom 0.1 to 0.5 ppm in synthetic air for 30 min at 37 degrees C. AMs we re fixed on a polycarbonate membrane and placed on culture medium. A c ulture was established, with the exposed AM (nonstimulated or stimulat ed with 1 mu g/ml lipopolysaccharide [LPS]), and the remaining cells w ere used to determine the cytokines. IL-1 beta, IL-6, and IL-8 were qu antified by commercial enzyme-linked immunosorbent assay kits (ELISA k its). TNF-alpha was determined with a ''sandwich'' ELISA, using the bi otin-streptavidin system. NO2 exposure of nonstimulated AM did not res ult in changes in IL-1 beta, IL-6, TNF-alpha, and TGF-beta release, co mpared to the situation with control experiments. Exposure for 30 min to NO2 induced a significant decrease of LPS-stimulated IL-1 beta, IL- 6, IL-8, and TNF-alpha (p <.05). The release of TGF-beta was not signi ficantly affected by NO2 exposure. Cytotoxicity of AM was checked by t rypan blue exclusion, with values ranging from 1.3 to 3.0%. NO2 exposu re of LPS-stimulated AM resulted in a functional impairment of AM afte r NO2 exposure regarding IL-1 beta, IL-6, IL-8, and TNF-alpha. Neither the spontaneous nor the stimulated release of TGF-beta were influence d by NO2.