Immunology of VIP: A Review and Therapeutical Perspectives

Abstract

Vasoactive intestinal peptide (VIP) is a neuropeptide with a broad distribution in the body that exerts very important pleiotropic functions in several systems. The present work reviews the immunology of VIP. Being daring, this neuropeptide could be included in the group of cytokines since it is produced and secreted by different immunocompetent cells in response to various immune signals, plays a broad spectrum of immunological functions, and exerts them, in a paracrine and/or autocrine way, through three different specific receptors. Although VIP has been classically considered as an immunodepressant agent, and its main described role has been as an anti-inflammatory factor, several evidences suggest that a better way to see this peptide is as a modulator of the homeostasis of the immune system. In the last decade, the pharmacology of VIP has spectacularly grown, and VIP itself, as well as more stable VIP-derived agents, have been used or proposed as efficient therapeutical treatments of several disorders, specially inflammatory and autoimmune diseases, such as septic shock, rheumatoid arthritis, multiple sclerosis, Crohn's disease and autoimmune diabetes. A broad field of perspectives is actually open, and further investigations will help us to definitively understand the immunology of this very important peptide.

Differential expression of vasoactive intestinal peptide and its functional receptors in human osteoarthritic and rheumatoid synovial fibroblasts

“…An abundant number of studies have consistently demonstrated potent immunomodulatory and antiinflammatory effects of exogenous administration of VIP (and related neuropeptides) in a variety of animal models of inflammatory disease, providing a solid basis for its potential use as a therapeutic agent (1)(2)(3)(6)(7)(8)(9)27). Several studies in the murine model of collagen-induced arthritis have shown that VIP or PACAP potently inhibits inflammatory and autoimmune components, protecting the joints from structural damage (5,6,28).…”

The neuropeptide genes TAC1, TAC3, TAC4, VIP and PACAP(ADCYAP1), and susceptibility to multiple sclerosis

“…Similarly, PACAP was reported to exert beneficial effects on clinical and pathological manifestations of EAE, probably through suppression of antigen presenting cell functions (Kato et al, 2004). VIP and PACAP exert a number of effects in the central nervous system (CNS) that could generally be regarded as being anti-inflammatory and neuroprotective (Gressens et al, 1997;Gozes et al, 1997;Gomariz et al, 2001). Upon axotomy, expression of PACAP is rapidly induced (Mulder et al, 1999).…”

Effect of inactivating mutations on phosphorylation and internalization of the human VPAC2 receptor

“…Vasoactive intestinal polypeptide (VIP) is a neuropeptide that contributes to regulation of intestinal secretion and motility, of exocrine and endocrine secretions (Fahrenkrug 1993), and to homeostasis of the immune system (Gomariz et al 2001). The effects of VIP are mediated through interaction with two receptor subclasses named VPAC 1 and VPAC 2 receptors .…”