Regulation of human alveolar macrophage inflammatory cytokine production by interleukin-10.
Alveolar macrophages are the primary source of inflammatory cytokine production in the lung. Both site-specific and differentiation-specific factors play a role in cytokine production, and regulation of this activity in alveolar macrophages is distinctly different from that of circulating blood monocytes. Interleukin-10 (IL-10) inhibits the production of inflammatory cytokines [tumor necrosis factor (TNF)-alpha, interleukin-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 undertaken to determine the effect of recombinant IL-10 on endotoxin-stimulated cytokine production by human alveolar macrophages. TNF, IL-1, IL-6, and IL-8 secretions were significantly (P < 0.05) stimulated by endotoxin [lipopolysaccharide (LPS)] and were all significantly (P < 0.05) inhibited (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 IL-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 production by human alveolar macrophages suggests that exogenous IL-10 may be useful in treatment of inflammatory lung diseases such as adult respiratory distress syndrome.
Thomassen
M J
MJ
Department of Pulmonary and Critical Care Medicine, Cleveland Clinic Foundation, Ohio 44195-5038, USA.
Divis
L T
LT
Fisher
C J
CJ
D016207:Cytokines / Q000096:biosynthesis*; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D016753:Interleukin-10 / Q000096:biosynthesis / Q000378:metabolism / Q000494:pharmacology*; D007376:Interleukin-2 / Q000096:biosynthesis; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D016207:Cytokines; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10