Indirect suppression of IL-7-responsive B cell precursors by vasoactive intestinal peptide.

Bone marrow is supplied with nerves and neuropeptides that influence a variety of cellular responses. This study represents an initial evaluation of vasoactive intestinal peptide (VIP) as a possible regulator of B lineage lymphocyte formation. As little as 10(-10) M concentrations of VIP inhibited the IL-7-driven clonal proliferation of pre-B cells in semisolid agar cultures. The response was blocked by a VIP antagonist and augmented by the ectoenzyme inhibitor, phosphoramidon. Suspensions of highly enriched B lineage precursors were unaffected by VIP unless they were cocultured with macrophage-like cells and conditioned medium from VIP-treated macrophages contained inhibitory activity. Neutralizing Abs were used to determine that IFN-alpha is at least one substance that is elicited by exposure of macrophages to VIP. These findings suggest that a neuropeptide can potentially modulate lymphopoiesis through a regulatory circuit that involves macrophages and IFN-alpha. They also raise the possibility that VIP can participate in antiviral defense.