Route of monocyte differentiation determines their cytokine production profile: CD40 ligation induces interleukin 10 expression.

Interleukin 10 is a potent anti-inflammatory and immunomodulatory cytokine. Little is known regarding its induction in monocytes/macrophages, however LPS, a reproducible trigger of IL-10, is augmented by direct contact with T cells. In this context, the role of CD40-ligation is investigated. In the rheumatoid synovium, IL-10 is produced by tissue macrophages. Monocytes primed with M-CSF, a cytokine present in rheumatoid joints, produced IL-1beta, TNF-alpha and IL-10 upon CD40-ligation at an IL-1: TNF-alpha: IL-10 ratio of 10:0.5:1. IFN-gamma-primed monocytes, however, predominantly produced TNF-alpha and IL-1beta. Both differentiated monocytes display an endogenous IL-10 activity regulatable by CD40 stimulation. Additionally, these monocytes display differential control by exogenous and endogenous IL-1 and TNF-alpha. M-CSF-primed monocyte IL-10 production was dependent on endogenous TNF-alpha and, to a lesser extent, IL-1, whereas IFN-gamma-primed monocytes were partially dependent on endogenous IL-1. The addition of exogenous IL-1 augments CD40 induced IL-10 production by IFN-gamma-primed monocytes. These data indicate that CD40 ligation regulates cell contact mediated macrophage IL-10 and that the route of differentiation determines the cytokine profile.