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

Eur J Immunol. 1990 Feb;20(2):253-7. doi: 10.1002/eji.1830200204.


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 controversial 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 1 beta led to similar conclusions, whereas measurement of IL 1 alpha by radioimmunoassay indicated, in addition, an increase in intracellular IL 1 alpha.

MeSH terms

  • Animals
  • Cells, Cultured
  • Complement C5a / pharmacology*
  • Drug Synergism
  • Histamine Release / drug effects
  • Humans
  • In Vitro Techniques
  • Interleukin-1 / metabolism*
  • Lipopolysaccharides
  • Macrophage Activation
  • Macrophages / metabolism*
  • Mice
  • Monocytes / metabolism*
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha / metabolism*


  • Interleukin-1
  • Lipopolysaccharides
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Complement C5a