INTERLEUKIN-10 INHIBITS ALVEOLAR MACROPHAGE PRODUCTION OF INFLAMMATORY MEDIATORS INVOLVED IN ADULT-RESPIRATORY-DISTRESS-SYNDROME

Background. Adult respiratory distress syndrome (ARDS) causes severe m orbidity and mortality in trauma patients. One potential method to att enuate the lung injury is to inhibit alveolar macrophage production of proinflammatory mediators. The purpose of this study was to investiga te the cellular mechanism of interleukin 10 (IL-10) inhibition on LPS- stimulated macrophage (M phi). We hypothesized that IL-10 inhibited ph ospholipase C signal pathways in M phi. IL-10 inhibition would be rest ored by calcium ionophores and protein kinase C (PKC) activation. Meth ods. Rabbit alveolar M phi were obtained by bronchoalveolar lavage. M phi were treated with Escherichia coli LPS (10 ng/ml) in the presence of various concentrations of human IL-10. Cell lysates and supernatant were analyzed for proagulants (PCA) and tumor necrosis factor (TNF), respectively. TNF mRNA expression of alveolar M phi was also measured by Northern Blot assay. Macrophage PGE(2) production was measured by E LISA. Results. IL-10 inhibited the production of both TNF and PCA by L PS-stimulated M phi. In addition, IL-10 also reduced TNF mRNA expressi on. Similarly, PGE, production by LPS-stimulated M phi was also attenu ated by IL-10. An increase in the intracellular [Ca2+] induced by A231 87 failed to reverse this IL-10-mediated inhibition. In comparison, ph orbol myristate acetate, a protein kinase C (PKC) activator, restored TNF and PCA production despite the presence of IL-10. Conclusions. IL- 10 inhibits M phi production of inflammatory mediators. This inhibitio n is, at least in part, mediated by modulating the PKC activity. (C) 1 998 Academic Press.