We investigated the effects of recombinant C5a on interleukin-6 (IL-6) production by peripheral blood mononuclear cells (PBMC) in vitro and compared them with the release of interleukin-1 (IL-1) and tumour necrosis factor (TNF). In a virtually lipopolysaccharide (LPS)-free culture system, C5a by itself did not induce any significant IL-6 translation. The IL-6 release in response to low amounts of LPS (500 pg/ml) or IL-1 beta, however, was markedly increased by the complement fragment. This enhancement of IL-6 synthesis was dose-dependent, reached its optimum at 5.8 x 10(-9)M rC5a and occurred regardless of the presence of serum components. At the level of transcription C5a by itself did not induce IL-6 gene expression, but in the presence of low amounts of LPS the stimulation of monocytes with C5a yielded an increase in IL-6 mRNA. The transcription of IL-1 beta, however, can be induced by C5a alone. These data are interesting, since they indicate a different regulation of IL-1 beta and IL-6 by the complement fragment C5a. Furthermore, we could show that the C5a-mediated IL-6 production influenced the synthesis of IgG rather than IgM in vitro. These results may be relevant for an understanding of the potentiating role of C5a in cytokine-dependent disease processes.