INDUCTION BY VASOACTIVE-INTESTINAL-PEPTIDE OF INTERFERON-ALPHA BETA SYNTHESIS IN GLIAL-CELLS BUT NOT IN NEURONS/

Vasoactive intestinal peptide (VIP), a 28-aminoacid peptide, plays a m ultifunctional neuromodulatory role in both peripheral and central ner vous systems. We have recently reported that VIP induces interferon (I FN) alpha/beta synthesis in human colon adenocarcinoma cell line HT-29 . It has been reported that VIP may counteract HIV-induced neuronal ce ll death; therefore, we postulated that the action of VIP may be media ted by a cascade regulation, involving the production of some cytokine s such as IFN. Here we demonstrate that primary cultures of rat mesenc ephalic neurons and glial cells respond differently to VIP. Thus VIP e nhanced 2'5' oligoadenylate (2'5'A) synthetase activity and inhibited vesicular stomatitis virus multiplication in glial cultures only. Howe ver, both cell cultures had functional adenylate cyclase coupled recep tors for VIP. The increase in 2'5'A synthetase activity in glial cultu res reached a maximum with 10(-6)M VIP and required cellular RNA and p rotein synthesis. Anti-IFN alpha/beta, but not anti-IFN gamma, antibod ies abolished the induction of the antiviral and 2'5'A synthetase acti vities by VIP in rat glial-enriched cultures, suggesting that these in ductions were mediated through IFN alpha/beta synthesis. Moreover, VIP or poly (i).poly (C12U) caused, in the glial cultures, the induction and secretion of an IFN of type alpha/beta with a titer value of 16 an d 32 units/ml respectively. In contrast, neither of these two substanc es was able to induce IFN synthesis in neurons, which were, however, s ensitive to IFN alpha/beta produced by VIP-treated glial cells. IFN pr oduced by VIP in glial cells may therefore play an important role in d efending the brain against viruses. (C) 1994 Wiley-Liss, Inc.