MODULATION OF CYTOKINE PRODUCTION IN ACTIVATED HUMAN MONOCYTES BY SOMATOSTATIN

The immunosuppressor effects of the widely distributed neuropeptide so matostatin were examined on purified peripheral blood human monocytes. Somatostatin, at concentrations thought to be physiologic (10-(10)-10 (-7) M), regulated monocyte/macrophage responses to (LPS) stimulation, as reflected by interleukin production. In particular, somatostatin h ad direct inhibitory effects on TNF-alpha, IL-1 beta, and IL-6 secreti on by LPS-activated monocytes, while the decrease on IL-8 synthesis wa s modulated mainly by the action of somatostatin on TNF-alpha and IL-1 beta. In fact, the addition of these two inflammatory cytokines to th e monocyte culture medium was able to induce IL-8 expression, as demon strated by mRNA analysis, also in presence of the neuropeptide. Althou gh somatostatin affected IL-8 production in an indirect way, it suppre ssed directly the chemotactic response of neutrophils to IL-8. Finally , somatostatin downregulation of monocyte activation was confirmed by the decrease of HLA-DR expression on cell plasmamembranes (52% versus 33%). Our results confirm that somatostatin exerts preferential effect s on the suppression of immunoreactions by modulating cytokine product ion and activity.