VIP AND PACAP ENHANCE IL-6 RELEASE AND MESSENGER-RNA LEVELS IN RESTING PERITONEAL-MACROPHAGES - IN-VITRO AND IN-VIVO STUDIES

Vasoactive intestinal peptide (VIP), a neuropeptide produced by lympho cytes has been previously reported to modulate cytokine expression in T lymphocytes. In this study, we investigated the effects of VIP and o f the structurally related neuropeptide pituitary adenylate cyclase-ac tivating polypeptide (PACAP38) on the production of IL-6 in unstimulat ed murine peritoneal macrophages. Both neuropeptides stimulate rapidly , specifically, and similarly the production of IL-6, exerting their a ction through two different receptor/signal transduction systems, i.e. , primarily through the binding to VIP1/PACAP receptor followed by ade nylate cyclase activation, and partially through the activation of pro tein kinase C following binding to PACAP-R. VIP and PACAP38 regulate t he production of IL-6 at a transcriptional level, affecting the de nov o synthesis of this cytokine. The stimulatory in vitro effect correlat es with the stimulation of IL-6 expression and release in vivo. These studies suggest that VIP/PACAP play a role in immune system homeostasi s, participating in the intricate cytokine network and controlling loc al immune responses. In addition, the understanding of the factors tha t regulate the expression and release of IL-6 by macrophages is import ant for the elucidation of the role of IL-6 in health and disease. (C) 1998 Elsevier Science B.V. All rights reserved.