Vasoactive intestinal peptide inhibits interleukin (IL)-2 and IL-4 production through different molecular mechanisms in T cells activated via the T cell receptor/CD3 complex

J Neuroimmunol. 1993 Oct;48(1):59-69. doi: 10.1016/0165-5728(93)90059-8.


The neuropeptide vasoactive intestinal peptide (VIP) has been reported previously to inhibit cell proliferation and interleukin (IL)-2 production in mitogen-stimulated T lymphocytes. In physiological conditions, T lymphocytes are specifically activated by antigen-binding through the T cell receptor (TCR). Here we report on the effect of VIP and related peptides on IL-2 and IL-4 production of murine T lymphocytes stimulated through the TCR. VIP inhibited IL-2 and IL-4 production (both at the level of protein concentration and biological activity) by unfractionated spleen cells or purified CD4+ T cells stimulated with either anti-CD3 monoclonal antibodies (mAbs) or with anti-CD3 mAbs plus phorbol esters. The inhibition was dose-dependent, and specific, since structurally related peptides such as secretin and glucagon had little or no inhibitory activity. VIP inhibited IL-2 and IL-4 production through different molecular mechanisms. IL-2 production was regulated at a transcriptional level through the downregulation of IL-2 mRNA, whereas the production of IL-4 was modulated at a posttranscriptional level.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / drug effects
  • Cell Line
  • Cyclic AMP / physiology
  • Female
  • Interleukin-2 / biosynthesis*
  • Interleukin-4 / biosynthesis*
  • Lymphocyte Activation*
  • Mice
  • Mice, Inbred BALB C
  • Receptor-CD3 Complex, Antigen, T-Cell / physiology*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*
  • Vasoactive Intestinal Peptide / pharmacology*


  • Interleukin-2
  • Receptor-CD3 Complex, Antigen, T-Cell
  • Interleukin-4
  • Vasoactive Intestinal Peptide
  • Cyclic AMP