REGULATION OF HUMAN ALVEOLAR MACROPHAGE INFLAMMATORY CYTOKINE PRODUCTION BY INTERLEUKIN-10

Alveolar macrophages are the primary source of inflammatory cytokine p roduction in the lung. Both site-specific and differentiation-specific factors play a role in cytokine production, and regulation df this ac tivity in alveolar macrophages is distinctly different from that of ci rculating blood monocytes. Interleukin-10 (IL-10) inhibits the product ion of inflammatory cytokines [tumor necrosis factor (TNF)-alpha, inte rleukin-1 (IL-1), interleukin-6 (IL-6), and interleukin-8 (IL-8)] and enhances production of interleukin-1-receptor antagonist (IL-1ra) from endotoxin-stimulated human monocytes, but the effect of IL-10 on such activity in alveolar macrophages is unknown. This study was undertake n to determine the effect of recombinant IL-10 on endotoxin-stimulated cytokine production by human alveolar macrophages. TNF, IL-1, IL-6, a nd IL-8 secretions were significantly (P < 0.05) stimulated by endotox in [lipopolysaccharide (LPS)] and were all significantly (P < 0.05) in hibited (median inhibition = 43%) by IL-10 (10 ng/ml). In contrast, IL -1ra was not stimulated by LPS and basal levels were not affected by I L-10. LPS also did not significantly elevate alveolar macrophage IL-10 secretion (<100 pg/ml) and basal levels were undetectable (<15 pg/ml) . This potent inhibitory activity of IL-10 on inflammatory cytokine pr oduction by human alveolar macrophages suggests that exogenous IL-10 m ay be useful in treatment of inflammatory lung diseases such as adult respiratory distress syndrome. (C) 1996 Academic Press, Inc.