Vasoactive intestinal peptide in the immune system: potential therapeutic role in inflammatory and autoimmune diseases

Abstract

Vasoactive intestinal peptide (VIP), a neuropeptide that is produced by lymphoid as well as neural cells, exerts a wide spectrum of immunological functions, controlling the homeostasis of the immune system through different receptors expressed in various immunocompetent cells. In the last decade, VIP has been clearly identified as a potent anti-inflammatory factor, which acts by regulating the production of both anti- and pro-inflammatory mediators. In this sense, VIP has been described to prevent death by septic shock, an acute inflammatory disease with a high mortality. In addition, VIP regulates the expression of co-stimulatory molecules, this being an action that may be related to modulating the shift toward Th1 and Th2 differentiation. We have recently reported that VIP prevents the deleterious effects of an experimental model of rheumatoid arthritis, by downregulating both inflammatory and autoimmune components of the disease. Therefore, VIP has been proposed as a promising candidate alternative treatment for acute and chronic inflammatory and autoimmune diseases such as septic shock, arthritis, multiple sclerosis, Crohn disease, or autoimmune diabetes.

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

“…Upon axotomy, expression of PACAP is rapidly induced (Mulder et al, 1999). VIP and PACAP, released by injured neurons act as "neuron survival factors" by downregulating synthesis of pro-inflammatory factors such as iNOS, IL-1β, TNF-α and chemokines by activated microglia (Delgado et al, 2002a(Delgado et al, ,b, 2003. Activated microglia have been implicated in early stages of myelin destruction in MS (Trapp et al, 1999a).…”

Diffuse Pharmacophoric Domains of Vasoactive Intestinal Peptide (VIP) and Further Insights into the Interaction of VIP with the N-terminal Ectodomain of Human VPAC1 Receptor by Photoaffinity Labeling with [Bpa6]-VIP

“…It controls a large array of biological functions in the brain and peripheral organs (1) and was shown recently to exert potent anti-inflammatory actions (2). The two cloned VIP receptors also bind with high affinity another neuropeptide, the pituitary adenylyl cyclase-activating peptide, and have been named VPAC 2 receptors thereby (3).…”

Tuning immune tolerance with vasoactive intestinal peptide: A new therapeutic approach for immune disorders

“…It is significant that the organism responds to an exacerbated inflammatory response by increasing the peripheral production of endogenous anti-inflammatory neuropeptides, such as VIP, in an attempt to restore the immune homeostasis [7,14,32,51]. In addition, the presence of VIP in barrier organs like skin and mucosal barriers of the gastrointestinal, genital and respiratory tracts suggests that this neuropeptide may be a key component of the innate immune system.…”

“…Even where synthetic agonists were designed specifically for VIP receptors, they were less effective than the natural peptide as antiinflammatory agents [1,15,32,51]. In any case, the focus on the use of natural peptides in therapy is not new, and may be a case of history repeating itself, since naturally occurring human compounds have often proved to have striking therapeutic value (e.g., insulin and cortisone).It is significant that the organism responds to an exacerbated inflammatory response by increasing the peripheral production of endogenous anti-inflammatory neuropeptides, such as VIP, in an attempt to restore the immune homeostasis [7,14,32,51]. In addition, the presence of VIP in barrier organs like skin and mucosal barriers of the gastrointestinal, genital and respiratory tracts suggests that this neuropeptide may be a key component of the innate immune system.…”