Hd. Byrnes et al., Macrophage inflammatory protein-3 beta enhances IL-10 production by activated human peripheral blood monocytes and T cells, J IMMUNOL, 163(9), 1999, pp. 4715-4720
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.