Interleukin 10 inhibits alveolar macrophage production of inflammatory mediators involved in adult respiratory distress syndrome

Background. Adult respiratory distress syndrome (ARDS) causes severe morbidity and mortality in trauma patients. One potential method to attenuate the lung injury is to inhibit alveolar macrophage production of proinflammatory mediators. The purpose of this study was to investigate the cellular mechanism of interleukin 10 (IL-10) inhibition on LPS-stimulated macrophage (M phi). We hypothesized that IL-10 inhibited phospholipase C signal pathways in M phi. IL-10 inhibition would be restored by calcium ionophores and protein kinase C (PKC) activation. Methods. 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 ELISA. Results. IL-10 inhibited the production of both TNF and PCA by LPS-stimulated M phi. In addition, IL-10 also reduced TNF mRNA expression. Similarly, PGE, production by LPS-stimulated M phi was also attenuated by IL-10. An increase in the intracellular [Ca2+] induced by A23187 failed to reverse this IL-10-mediated inhibition. In comparison, phorbol 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 inhibition is, at least in part, mediated by modulating the PKC activity. (C) 1998 Academic Press.