Recombinant C5a enhances interleukin 1 and tumor necrosis factor release by lipopolysaccharide‐stimulated monocytes and macrophages

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Abstract
Lipopolysaccharide (LPS) is a potent inducer of interleukin 1 (IL 1) synthesis and release, and of tumor necrosis factor (TNF) secretion. Many signals can enhance the LPS‐induced production of these cytokines. We have previously observed that addition of low amounts of normal human serum to the culture medium enhances IL 1 production. Among serum factors, anaphylatoxins C3a and C5a and/or their desArg derivatives have been shown to enhance LPS‐induced IL 1 and TNF production. However, the capacity of natural anaphylatoxins to induce by themselves the production of cytokines remains a controversal issue. We have investigated the capacity of human recombinant C5a (hrC5a) to induce IL 1 and TNF production. Despite its lack of direct triggering, hrC5a was able to act synergistically with LPS, leading to higher IL 1 and TNF release by human monocytes and mouse peritoneal macrophages. As assessed by the comitogenic assay, hrC5a increased IL 1 release, whereas cell‐associated IL 1 activity was not significantly modified. Measurement by enzyme‐linked immunosorbent assay of human IL 1β led to similar conclusions, whereas measurement of IL 1α by radioimmunoassay indicated, in addition, an increase in intracellular IL 1α.

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