Interferon gamma inhibits interleukin 10 production by monocytes.
Interleukin 10 (IL-10) was first described for its ability to inhibit interferon gamma (IFN-gamma) production. Herein, we studied the balance between IFN-gamma and IL-10 production by human peripheral blood mononuclear cells (PBMC) in response to Staphylococcus aureus Cowan (SAC) or lipopolysaccharide (LPS). Monocyte depletion reduced IL-10 production by 90% and resulted in an increased IFN-gamma production. Addition of anti-IL-10 antibody to PBMC cultures also strongly increased IFN-gamma production. In contrast, among various cytokines, only IFN-gamma strongly reduced IL-10 synthesis by SAC- or LPS-activated PBMC and monocytes. Thus, IFN-gamma has proinflammatory effects through the combination of two mechanisms: (a) induction of early tumor necrosis factor alpha (TNF-alpha) and IL-1 beta synthesis; and (b) inhibition of the delayed production of IL-10, an inhibitor of TNF-alpha and IL-1 beta synthesis. Taken together, the present data indicate that IFN-gamma and IL-10 antagonize each other's production and function.
Chomarat
P
P
Laboratory for Immunological Research, Schering-Plough, Dardilly, France.
Rissoan
M C
MC
Banchereau
J
J
Miossec
P
P
D002478:Cells, Cultured; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000502:physiology*; D016753:Interleukin-10 / Q000037:antagonists & inhibitors / Q000502:physiology*; D009000:Monocytes / Q000378:metabolism*
D016753:Interleukin-10; D007371:Interferon-gamma