Both C3a and C3a(desArg) regulate interleukin-6 synthesis in human peripheral blood mononuclear cells.
Synthesis of complement components is part of the acute-phase response. Interleukin-6 (IL-6) is a critical mediator of the acute-phase response during infections and injuries. Plasma levels of C3a and IL-6 have been proposed as prognostic indicators in sepsis and trauma. The effects of C3a and C3a(des)Arg on IL-6 gene expression and protein production in human peripheral blood mononuclear cells (PBMC) were investigated. Neither C3a nor C3a(des)Arg alone induced detectable IL-6 protein or mRNA levels. However, C3a and C3a(des)Arg affected endotoxin-induced IL-6 synthesis in a dose-dependent manner. In nonadherent PBMC, C3a or C3a(des)Arg suppressed, while in adherent PBMC, C3a or C3a(des)Arg enhanced IL-6 protein and mRNA levels. These results suggest that C3a and C3a(des)Arg may provide a control mechanism of acute-phase responses by enhancing IL-6 synthesis in adherent monocytes at local inflammatory sites and by inhibiting IL-6 synthesis in circulating monocytes.
Takabayashi
T
T
Tupper Research Institute, Department of Medicine, Tufts University School of Medicine and New England Medical Center, Boston, Massachusetts 02111, USA.
Vannier
E
E
Burke
J F
JF
Tompkins
R G
RG
Gelfand
J A
JA
Clark
B D
BD
D002448:Cell Adhesion; D002478:Cells, Cultured; D015926:Complement C3a / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008934:Mitogens / Q000494:pharmacology; D012333:RNA, Messenger
D015850:Interleukin-6; D008070:Lipopolysaccharides; D008934:Mitogens; D012333:RNA, Messenger; C044541:complement C3a, des-Arg-(77)-; D015926:Complement C3a