VASOACTIVE-INTESTINAL-PEPTIDE DOWN-REGULATES THE EXPRESSION OF IL-2 BUT NOT OF IFN-GAMMA FROM STIMULATED MURINE T-LYMPHOCYTES

The neuropeptide vasoactive intestinal peptide (VIP) has been previous ly reported to inhibit T cell proliferation. Here we report on the eff ect of VIP on IL-2 and on IFNgamma production by murine T lymphocytes stimulated with mitogens (ConA), or activated through the antigen-spec ific T cell receptor. VIP inhibited IL-2 production by either unfracti onated spleen cells, or by purified CD4+ T cells in a dose-dependent m anner. The effect was specific, since structurally related peptides su ch as secretin and glucagon had little or no inhibitory effect. VIP in duced a rapid increase in intracellular cAMP in CD4+ T cells, suggesti ng that the inhibitory effect of VIP could be mediated through the ind uction of cAMP. Northern blots showed that VIP downregulated IL-2 mRNA , indicating the occurrence of a transcriptional regulatory event. In contrast with its effect on IL-2, VIP did not affect IFNgamma producti on by either mitogen-stimulated normal T lymphocytes, or by the L12R4 murine T cell line which produces IFNgamma in response to PMA stimulat ion.