Interleukin 10 inhibits the release of CC chemokines during human endotoxemia

Sixteen healthy subjects were intravenously injected with lipopolysaccharide (LPS), once with placebo and once with recombinant human interleukin OL)-10 (25 mu g/kg), to determine the effect of IL-10 on LPS-induced production of macrophage inflammatory protein (MIP)-1 alpha, MIP-1 beta, and monocyte chemoattractant protein (MCP)-1. LPS induced transient increases in serum MIP-1 alpha, MIP-1 beta, and MCP-1. Pretreatment with IL-10 inhibited LPS-induced release of MIP-1 alpha, MIP-1 beta, and MCP-1, Ln whole blood in vitro, the IL-10-induced inhibition of MTP-1 alpha and MIP-1 beta release was equally potent in the presence or absence of an anti-tumor necrosis factor (TNF) antibody. Although isolated peripheral blood mononuclear cells produced more MIP-1 alpha and MIP-1 beta than neutrophils, the latter cells were more sensitive to the inhibiting effect of IL-10, IL-10 attenuates LPS-induced production of CC chemokines in human endotoxemia, whereby in vitro experiments suggest that, in the case of MIP-1 alpha and MIP-1 beta release, this effect is independent from an inhibitory effect on TNF production.