Macrophage inflammatory protein-3 beta enhances IL-10 production by activated human peripheral blood monocytes and T cells

We report that the addition of human macrophage inflammatory protein-3 beta (MIP-3 beta) to cultures of human PBMCs that have been activated with LPS o r PHA results in a significant enhancement of IL-10 production. This effect was concentration-dependent,,vith optimal MIP-3 beta concentrations induci ng 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 si gnificant effect on IL-10 production was observed when 6Ckine, the other re ported ligand for human CCR7, or other CC chemokines such as monocyte chemo attractant protein-1, RANTES, MIP-1 alpha, and MIP-1 beta were added to LPS - or PHA-stimulated PBMCs, Similar results were observed using activated pu rified human;peripheral blood monocytes or T cells. Addition of MIP-3 beta to nonactivated PBMCs: had no effect on cytokine production. Enhancement of IL-10 production by MIP-3 beta correlated with the inhibition of IL-12 p40 and TNF-alpha production by monocytes and with the impairment of IFN-gamma production by T cells, which was reversed by addition of anti-IL-10 Abs to the cultures. The ability of MIP-3 beta to augment IL-10 production correl ated with CCR7 mRNA expression and stimulation of intracellular Calcium mob ilization in both monocytes and T cells. These data indicate that MIP-3 bet a acts directly on human monocytes and T cells and suggest that this chemok ine is unique among ligands binding to CC receptors due to its ability to m odulate inflammatory activity via the enhanced production of the anti-infla mmatory cytokine IL-10.