Vasoactive intestinal peptide, pituitary adenylate cyclase-activating polypeptide and immune system: from basic research to potential clinical application

Abstract

Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) are important immune me­ diators sharing cellular origin, receptors and functions affecting both the innate and the acquired immunity. VIP and PACAP have been clearly identified as potent antiinflammatory factors, which act by regulating the production of both anti- and pro- inflammatory mediators. In this context, both peptides have been described to prevent death by septic shock, an acute high mortality inflammatory disease. Additionally, VIP and PACAP regulate the expression of costimulatory molecules, an action that may be related to modulating the shift toward Th1 and Th2 differentiation. We have recently reported that both peptides prevent the deleterious effects of an experimental model of rheumatoid arthritis, by downregulating both inflammatory and autoimmune components of the disease. Thus, VIP and PACAP represent potential multistep therapeutic agents that provide the mechanisms to act at different levels in the complex network cascade formed by chemokines and cytokines involved in the regulation of inflammatory/Th1 diseases. Based on the protective effects of VIP and PACAP we conclude that the exogenous administration of these peptides could offer an alternative to existing treatments for arthritis and other inflammatory/Th1-autoimmune diseases, such as multiple sclerosis, inflammatory bowel disease, or autoimmune diabetes, as well as endotoxic shock. Biomedical Reviews 2001; 12: 1-9.