Interferon gamma inhibits interleukin 10 production by monocytes

doi:10.1084/jem.177.2.523

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Interferon gamma inhibits interleukin 10 production by monocytes

P Chomarat, MC Rissoan, J Banchereau and P Miossec
Laboratory for Immunological Research, Schering-Plough, Dardilly, France.

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.
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