BOTH C3A AND C3A(DESARG) REGULATE INTERLEUKIN-6 SYNTHESIS IN HUMAN PERIPHERAL-BLOOD MONONUCLEAR-CELLS

Synthesis of complement components is part of the acute-phase response . Interleukin-6 (IL-6) is a critical mediator of the acute-phase respo nse during infections and injuries. Plasma levels of C3a and IL-6 have been proposed as prognostic indicators in sepsis and trauma. The effe cts of C3a and C3a(desArg) on IL-6 gene expression and protein product ion in human peripheral blood mononuclear cells (PBMC) were investigat ed. Neither C3a nor C3a(desArg) alone induced detectable IL-6 protein or mRNA levels. However, C3a and C3a(desArg) affected endotoxin-induce d IL-6 synthesis in a dose-dependent manner. In nonadherent PBMC, C3a or C3a(desArg) suppressed, while in adherent PBMC, C3a or C3a(desArg) enhanced IL-6 protein and mRNA levels. These results suggest that C3a and C3a(desArg) may provide a control mechanism of acute-phase respons es by enhancing IL-6 synthesis in adherent monocytes at local inflamma tory sites and by inhibiting IL-6 synthesis in circulating monocytes.