INDIRECT SUPPRESSION OF IL-7-RESPONSIVE B-CELL PRECURSORS BY VASOACTIVE-INTESTINAL-PEPTIDE

Pone marrow is supplied with nerves and neuropeptides that influence a variety of cellular responses. This study represents an initial evalu ation of vasoactive intestinal peptide (VIP) as a possible regulator o f B lineage lymphocyte formation. As little as 10(-10) M concentration s of VIP inhibited the IL-7-driven clonal proliferation of pre-B cells in semisolid agar cultures. The response was blocked by a VIP antagon ist and augmented by the ectoenzyme inhibitor, phosphoramidon. Suspens ions of highly enriched B lineage precursors were unaffected by VIP un less they were cocultured with macrophage-like cells and conditioned m edium from VIP-treated macrophages contained inhibitory activity. Neut ralizing Abs were used to determine that IFN-cu is at least one substa nce that is elicited by exposure of macrophages to VIP. These findings suggest that a neuropeptide can potentially modulate lymphopoiesis th rough a regulatory circuit that involves macrophages and IFN-alpha. Th ey also raise the possibility that VIP can participate in antiviral de fense.