Human recombinant C5a enhances lipopolysaccharide‐induced synthesis of interleukin‐6 by human monocytes

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Abstract
The effect of human recombinant C5a (hrC5a) on the synthesis of interleukin‐6 (IL‐6) was studied in human monocytes. Monocytes incubated in the absence of hrC5a and of bacterial lipopolysacchar‐ide (LPS) produced only low amounts (< 100 U/ 2×106 cell/16 h) of IL‐6 activity. LPS in concentrations from 10 pg ml‐1 to 10 ng ml‐1 greatly stimulated the synthesis of IL‐6 to about 50.000 U/106 cells/16 h. When hrC5a was added to the monocyte media maximal IL‐6 synthesis was reached at lower LPS concentrations, i.e. at 0.1 ng ml‐1 LPS in the presence of 100 ng ml‐1 hrC5a. Maximal IL‐6 production was not significantly enhanced by hrC5a. Metabolic labelling with [35S]‐methionine followed by immunoprecipi‐tation of IL‐6 showed that the increased IL‐6 activity in the medium of hrC5a treated monocytes was due to a stimulation of the de novo synthesis of IL‐6. Increased amounts of IL‐6 mRNA were found in monocytes treated with LPS and hrC5a compared with monocytes stimulated only with LPS. HrC5a prolonged the elevation of IL‐6 mRNA levels after stimulation of monocytes with LPS. HrC5a thus enhanced the LPS‐induced synthesis of IL‐6 by human monocytes.