Therapeutical Approaches of Vasoactive Intestinal Peptide as a Pleiotropic Immunomodulator

Abstract

The vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) are two neuropeptides belonging to the VIP/secretin/glucagon family of peptides. VIP/PACAP are present and released from both innervation and immune cells, particularly Th2 cells, and exert a wide spectrum of immunological functions controlling the homeostasis of immune system through different receptors expressed in various immunocompetent cells. VIP/PACAP have a general anti-inflammatory effect, both in innate and adaptive immunity. In innate immunity, VIP/PACAP inhibit the production of pro-inflammatory cytokines and chemokines from macrophages, microglia and dendritic cells. In addition, VIP/PACAP reduce the expression of costimulatory molecules (particularly CD80 and CD86) on the antigen-presenting cells, and therefore reduce stimulation of antigen-specific CD4(+) T cells. In terms of adaptive immunity, VIP/PACAP promote Th2-type responses, and reduce the pro-inflammatory Th1-type responses. Several of the molecular mechanisms involved in the inhibition of cytokine and chemokine expression, and in the preferential development and/or survival of Th2 effectors, are perfectly known. Therefore, VIP/PACAP and analogues have been recently proposed as very promising candidates, alternative to other existing treatments, for treating acute and chronic inflammatory and autoimmune diseases, such as septic shock, rheumatoid arthritis, multiple sclerosis, Parkinson's disease, Crohn disease, or autoimmune diabetes. The aim of this review is firstly to update our knowledge of the cellular and molecular events relevant to VIP function on the immune system; and secondly to gather together recent data that support its role as a type 2 cytokine. Recognition of the central functions VIP plays in cellular processes is focusing our attention on this "very important peptide" as an exciting new candidate for therapeutic intervention and drug development.

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

“…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). …”

Neuronal pathways in tendon healing and tendinopathy - update

“…This observation may reflect that NA and NPY (vasoconstrictive) predominantly regulate the main blood flow to the tendon proper, whereas VIP (vasodilatory) is responsible for the fine-tuning of blood flow at a microlevel (58). The non-vascular distribution of VIP would seem to comply with an anti-inflammatory effect in the periphery ( Figure 1C) (69)(70)(71). The strong anti-inflammatory role of VIP has been suggested to act through inhibition of T cell proliferation and migration (64,(71)(72)(73).…”

VIP (vasoactive intestinal peptide)

“…In the pituitary, VIP gene expression is regulated by estrogen leading to altered prolactin secretion (Montagne et al, 1995). VIP is present in and secreted from immune cells especially Th2 cells altering cytokine and chemokine production (Gonzalez-Rey et al, 2007). The VIP gene is in NSCLC cells and its expression is regulated in a PKC and cAMP dependent manner (Davidson et al, 1996).…”