CALCITONIN-GENE-RELATED PEPTIDE INHIBITS PROLIFERATION AND ANTIGEN PRESENTATION BY HUMAN PERIPHERAL-BLOOD MONONUCLEAR-CELLS - EFFECTS ON B7, INTERLEUKIN-10, AND INTERLEUKIN-12

CGRP is a neuropeptide that has previously been described to possess i mmunosuppressive activities, CGRP is released from peripheral nerves t hat, in the skin, are in close physical association with dendritic APC , We sought to investigate the mechanisms by which CGRP can inhibit im mune responses by studying its effects on human peripheral blood monon uclear cells (PBMC), Using allogeneic monocytes as stimulator cells, C GRP could inhibit the proliferation of PBMC by 47% when CGRP was prese nt for the duration of culture, Interestingly, when the stimulator mon ocytes were incubated with CGRP for 2 h prior to irradiation then wash ed, the observed inhibition increased to 85%, suggesting that CGRP was exerting a direct effect on the monocyte stimulator population, Final ly, the recall response to tetanus toroid (TT) by PBMC from individual s vaccinated with TT 14 d prior was inhibited by 25-50% in the presenc e of CGRP, Also, CGRP decreased the levels of B7.2 but not B7.1 on tre ated monocytes, and this inhibition could be abrogated by the addition of anti-IL-10 antibody, suggesting that the inhibition was mediated b y an increase in IL-10 production, Moreover, increased IL-10 productio n was confirmed by ELISA, Both IL-12 p40 and IFN-gamma levels in CGRP- treated cultures were found to be decreased by approximately 30%, The decrease in IL-12 p40 levels could be reversed by addition of anti-IL- 10, These data suggest that CGRP inhibits PBMC proliferation, in part, through the release of IL-10, which in turn can downregulate importan t co-stimulatory molecules and the cytokines IL-12 and IFN-gamma.