Regulatory role of C5a in LPS-induced IL-6 production by neutrophils during sepsis. Academic Article uri icon


  • Experimental sepsis in rodents occurring after cecal ligation/puncture (CLP) is associated with excessive complement activation and a systemic inflammatory response. The proinflammatory mediator IL-6 has recently been shown to be an important inducer of the C5a receptor (C5aR) during sepsis. We now provide evidence that serum IL-6 production during sepsis in rats was reduced in neutrophil-depleted animals and that absence of C5aR in mice as well as antibody-blockade of C5a in rats significantly reduced serum levels of IL-6 during sepsis. Lipopolysaccharide (LPS)-induced production in vitro of IL-6 by neutrophils was significantly enhanced in the co-presence of C5a, likely due to transcriptional up-regulation of IL-6. Production of IL-6 in neutrophils by LPS was NF-kappaB dependent (but not on the presence of p50) and dependent on phosphorylation of p38-mitogen activated protein kinase (MAPK) as well as p44/p42 MAPK (ERK1/2) but not on phosphorylation of c-Jun N-terminal kinases (JNK1/2). C5a stimulation of neutrophils elicited a rapid phosphorylation of ERK1/2 and p38 MAPK. Accordingly, we suggest that induction of IL-6 after CLP is neutrophil and C5a/C5aR dependent, likely due to the ability of C5a to cause activation of ERK1/2 and p38 MAPK signaling pathways.

published proceedings


altmetric score

  • 3

author list (cited authors)

  • Riedemann, N. C., Guo, R., Hollmann, T. J., Gao, H., Neff, T. A., Reuben, J. S., ... Ward, P. A

citation count

  • 133

complete list of authors

  • Riedemann, Niels C||Guo, Ren-Feng||Hollmann, Travis J||Gao, Hongwei||Neff, Thomas A||Reuben, Jayne S||Speyer, Cecilia L||Sarma, J Vidya||Wetsel, Rick A||Zetoune, Firas S||Ward, Peter A

publication date

  • February 2004