VIP–PACAP System in Immunity

Abstract

Our research about VIP/PACAP and the immune system goes back to 1990 when our group described the expression of VIP on lymphocytes for the first time. Since this year, using three models of disease, septic shock, rheumathoid arthritis, and Crohn's disease, we are trying to contribute with new pieces to the puzzle of immunity to approach the use of VIP/PACAP system as a therapeutic agent. In 1999 we established that the first step in the beneficial effect of the VIP/PACAP system exerts consists in its potent anti-inflammatory action. Thus, VIP and PACAP inhibit the expression and release of proinflammatory cytokines and chemokines, and enhance the production of the anti-inflammatory factors. These effects were reported both in vitro and in vivo, are mediated by the presence of PAC1, VPAC1, and VPAC2 receptors, in the three models of diseases used. The next step was that the system favors Th2 responses versus Th1 contributing to the remission of illness as rheumatoid arthritis or Crohn's disease by blocking the autoimmune component of these diseases. Because it appears that inflammatory processes requires more than blockade of a single mediator, new therapies blocking several components of both the infection- and the autoimmunity-induced inflammation cascades should be an interesting focus of attention. In this sense, at present we are trying to dissect new aspects of the potential therapeutic of the VIP/PACAP system in the control of CC and CXC chemokine and their receptors, coagulation factors, adhesion molecules, acute phase proteins, and osteoclastogenesis mediators as well as in the modulation of the expression of Toll-like receptors. Our more recent data open a hopeful door for the therapeutic use of VIP/PACAP in humans.

Vasoactive intestinal peptide/vasoactive intestinal peptide receptor relative expression in salivary glands as one endogenous modulator of acinar cell apoptosis in a murine model of Sjögren's syndrome

“…The lower levels of NOS activity were found in glands of 16-week-old NOD mice that presented increased apoptosis of acinar cells and increased levels of tumour necrosis factor (TNF)-a, among other T helper type 1 (Th1) cytokines in the serum [15,16]. Vasoactive intestinal peptide (VIP), described initially as a vasodilator and prosecretory neuropeptide, has trophic effects on acini [17,18] and strong anti-inflammatory properties in several models of chronic inflammatory diseases [19][20][21]. Prediabetic NOD mice treated systemically with VIP showed increased serum interleukin (IL)-10 and reduced Th1 cytokine levels [22] while gene-transfer of VIP onto NOD submandibular glands prevented saliva secretion loss and partly reduced glandular Th1 cytokine expression [23].…”

Pituitary Adenylate Cyclase-Activating Polypeptide and Its Receptors: 20 Years after the Discovery

“…These observations suggest that PACAP may regulate in vivo the proliferation of these subsets of CD4 ϩ T cells. Through its action on cytokines, chemokines, cell adhesion molecules, and costimulatory molecules produced or expressed by activated antigen-presenting cells, and through its direct and/or indirect effects on Th cell responses, PACAP appears as an important endogenous immunomodulatory molecule that exerts protective anti-inflammatory actions in many different models of autoimmune diseases (Abad et al, 2001;Gomariz et al, 2006). Based on these observations, VIP and PACAP are currently raising interest as candidates for development into new therapeutically valuable anti inflammatory agents (Delgado et al, 1999b(Delgado et al, , 2000Gonzalez-Rey et al, 2007;Tan et al, 2009).…”

NOD Mice Exocrinopathy: Towards a Neuroimmune Link

“…It also controlled inflammation in models of rheumatoid arthritis, Crohn's disease and diabetes [13,15] .…”

“…VIP is a neuro-and immunopeptide that promotes secretion, contributes to vasodilation in exocrine glands [12] and promotes anti-inflammatory effects in normal mouse-activated macrophages by inhibiting NOS induction while stimulating IL-10 [13,14] . It also controlled inflammation in models of rheumatoid arthritis, Crohn's disease and diabetes [13,15] .…”