Divergent roles of tumor necrosis factor and platelet-activating factor in endotoxin-induced release of monocyte chemoattractant protein 1 and macrophage inflammatory protein 1beta in chimpanzees

Abstract

A platelet-activating factor receptor antagonist reduced the release of macrophage inflammatory protein 1beta (MIP-1beta) during endotoxemia in chimpanzees but did not influence the secretion of monocyte chemoattractant protein 1 (MCP-1). Anti-tumor necrosis factor alpha monoclonal antibody completely prevented MCP-1 release and simultaneously enhanced the secretion of MIP-1beta. Levels of MIP-1beta and MCP-1 release were differentially regulated during endotoxemia.

FIG. 1

Effect of inhibition of PAF on endotoxin-induced MCP-1 and MIP-1β release. Mean (± SE) concentrations of MCP-1 (upper panel) and MIP-1β (lower panel) in sera after intravenous injection of chimpanzees with E. coli endotoxin (4 ng/kg) at time zero. Filled squares, injection of endotoxin only (n = 6); open circles, injection of endotoxin with simultaneous infusion of the PAF antagonist TCV-309 (n = 4). P values indicate differences in results between treatment groups. NS, not significant.

FIG. 2

Effect of neutralization of TNF on endotoxin-induced MCP-1 and MIP-1β release. Mean (± SE) concentrations of MCP-1 (upper panel) and MIP-1β (lower panel) in sera after intravenous injection of chimpanzees with E. coli endotoxin (4 ng/kg) at time zero. Filled squares, injection of endotoxin only (n = 6); open circles, injection of endotoxin directly followed by injection of anti-TNF MAb; closed circles, injection of endotoxin followed after 30 min by injection of anti-TNF MAb. In the upper panel, the P value applies to the results of both anti-TNF MAb treatments (for the difference with endotoxin only). In the lower panel, the significance applies only to the results when anti-TNF MAb was given directly after endotoxin (for the difference with endotoxin only).