INTERLEUKIN-1-MEDIATED RELEASE OF INTERLEUKIN-8 BY ASBESTOS-STIMULATED HUMAN PLEURAL MESOTHELIAL CELLS

The pleuropulmonary response to inhaled asbestos frequently involves i nflammation and release of various cytokines from lung cells. Among th ese, interleukin-8 (IL-8) released from the mesothelium could augment inflammation of the pleura by attracting neutrophils to the pleural sp ace. We used cultures of human pleural mesothelial cells (HPMC) to exa mine the mechanism of IL-8 production by asbestos and cytokines. Suspe nsions of amosite, chrysotile, or crocidolite asbestos in concentratio ns as low as 5 mu g/ml enhanced release of IL-8 from HPMC during 6 h o f incubation at 37 degrees C. Electron microscopy of asbestos-treated HPMC showed that the cells avidly engulfed each of the different types of asbestos fibers. Two proinflammatory cytokines, interleukin-1 alph a (IL-1 alpha) and tumor necrosis factor-or, enhanced IL-8 release wit hin 2 h and had an even greater effect after 6 h. Release of IL-8 was measured by an enzyme-linked immunosorbent assay, and functional activ ity of the cytokine was assessed by chemotaxis of human neutrophils. I dentity of IL-8 in HPMC supernatants was established by absorption wit h an antibody to IL-8. Preincubation of HPMC with IL-1 receptor antago nist (IL-1ra) significantly decreased release of IL-8 after stimulatio n with amosite or crocidolite asbestos. We conclude that HPMC release IL-8 in response to asbestos stimulation and that the response is, in part, mediated by IL-1, mainly in the form of IL-1 alpha.