C5a-mediated release of interleukin 6 by human monocytes.
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.
Scholz
W
W
Immunetech Pharmaceuticals, San Diego, California 92121.
McClurg
M R
MR
Cardenas
G J
GJ
Smith
M
M
Noonan
D J
DJ
Hugli
T E
TE
Morgan
E L
EL
D015936:Complement C5a / Q000494:pharmacology*; D004731:Endotoxins / Q000502:physiology; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology
D004731:Endotoxins; D015850:Interleukin-6; D012333:RNA, Messenger; D011994:Recombinant Proteins; D015936:Complement C5a