Macrophage Inflammatory Protein-3β Enhances IL-10 Production by Activated Human Peripheral Blood Monocytes and T Cells

Abstract

AbstractWe report that the addition of human macrophage inflammatory protein-3β (MIP-3β) to cultures of human PBMCs that have been activated with LPS or PHA results in a significant enhancement of IL-10 production. This effect was concentration-dependent, with optimal MIP-3β concentrations inducing more than a 5-fold induction of IL-10 from LPS-stimulated PBMCs and a 2- to 3-fold induction of IL-10 from PHA-stimulated PBMCs. In contrast, no significant effect on IL-10 production was observed when 6Ckine, the other reported ligand for human CCR7, or other CC chemokines such as monocyte chemoattractant protein-1, RANTES, MIP-1α, and MIP-1β were added to LPS- or PHA-stimulated PBMCs. Similar results were observed using activated purified human peripheral blood monocytes or T cells. Addition of MIP-3β to nonactivated PBMCs had no effect on cytokine production. Enhancement of IL-10 production by MIP-3β correlated with the inhibition of IL-12 p40 and TNF-α production by monocytes and with the impairment of IFN-γ production by T cells, which was reversed by addition of anti-IL-10 Abs to the cultures. The ability of MIP-3β to augment IL-10 production correlated with CCR7 mRNA expression and stimulation of intracellular calcium mobilization in both monocytes and T cells. These data indicate that MIP-3β acts directly on human monocytes and T cells and suggest that this chemokine is unique among ligands binding to CC receptors due to its ability to modulate inflammatory activity via the enhanced production of the anti-inflammatory cytokine IL-10.