C5a-mediated release of interleukin 6 by human monocytes

Clin Immunol Immunopathol. 1990 Nov;57(2):297-307. doi: 10.1016/0090-1229(90)90043-p.


Recombinant human C5a (rC5a) was assessed for its ability to induce interleukin 6 (IL-6) production in human peripheral blood-derived mononuclear cell (PBMC) cultures. rC5a was observed to induce IL-6 production as measured by hybridoma growth promotion (B9.9 assay) and human B cell differentiation (SKW6.4 assay). Optimal IL-6 production was obtained after 24 hr stimulation with 0.1-0.5 micrograms/ml rC5a. In addition, natural human C5ades Arg and natural porcine C5a were able to induce a similar level of IL-6. The observed IL-6 activity appeared not to be due to endotoxin contamination since heat treatment (100 degrees C/15 min) inhibited rC5a induction of IL-6. The rC5a stimulation also induced an increase in steady-state IL-6 mRNA as determined by Northern blot analysis. Pretreatment of PBMC with leucine-methyl ester to deplete monocytes reduced the rC5a-induced IL-6 production to background levels. In addition, stimulation of purified T cell preparations with rC5a produced little IL-6 activity, suggesting that monocytes are the major source of IL-6 in this system. These results suggest that the inflammatory and immunoregulatory activities of C5a may in part be due to the stimulation of IL-6 release, a cytokine which possesses potent pleiotropic functions.

MeSH terms

  • Complement C5a / pharmacology*
  • Endotoxins / physiology
  • Humans
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism*
  • Monocytes / metabolism*
  • RNA, Messenger / metabolism
  • Recombinant Proteins / pharmacology


  • Endotoxins
  • Interleukin-6
  • RNA, Messenger
  • Recombinant Proteins
  • Complement C5a