A Clinical Approach for the Use of VIP Axis in Inflammatory and Autoimmune Diseases

Abstract

The neuroendocrine and immune systems are coordinated to maintain the homeostasis of the organism, generating bidirectional communication through shared mediators and receptors. Vasoactive intestinal peptide (VIP) is the paradigm of an endogenous neuropeptide produced by neurons and endocrine and immune cells, involved in the control of both innate and adaptive immune responses. Exogenous administration of VIP exerts therapeutic effects in models of autoimmune/inflammatory diseases mediated by G-protein-coupled receptors (VPAC1 and VPAC2). Currently, there are no curative therapies for inflammatory and autoimmune diseases, and patients present complex diagnostic, therapeutic, and prognostic problems in daily clinical practice due to their heterogeneous nature. This review focuses on the biology of VIP and VIP receptor signaling, as well as its protective effects as an immunomodulatory factor. Recent progress in improving the stability, selectivity, and effectiveness of VIP/receptors analogues and new routes of administration are highlighted, as well as important advances in their use as biomarkers, contributing to their potential application in precision medicine. On the 50th anniversary of VIP’s discovery, this review presents a spectrum of potential clinical benefits applied to inflammatory and autoimmune diseases.

Lasting and Sex-Dependent Impact of Maternal Immune Activation on Molecular Pathways of the Amygdala

“…The over-expression of the neuropeptide receptor VIPR2 in the amygdala of MPA relative to CON females (Table 1) is consistent with reports that duplications in this gene confer a significant risk for SSD (Morris and Pratt, 2014). The differential expression of the VIP receptor is particularly important because GABAergic interneurons in the amygdala express the neuropeptide VIP that facilitates cell firing (Rhomberg et al, 2018) and maintains the balance of pro-and anti-inflammatory cytokines (Martinez et al, 2020). The under-expression of GPX3 in MPA relative to CON males (Table 1) is consistent with the association between GPX3 gene expression and SSD (Zhao et al, 2018).…”

Proteomic Analysis of Synovial Fibroblasts and Articular Chondrocytes Co-Cultures Reveals Valuable VIP-Modulated Inflammatory and Degradative Proteins in Osteoarthritis

“…Joint tissues are sources of bioactive neuropeptides, such as neuropeptide Y, pituitary adenylate cyclase-activating polypeptide and vasoactive intestinal peptide (VIP) that induces changes in the cell metabolism in degenerative conditions such as OA [ 19 ]. VIP and its G protein-coupled receptors (GPCRs), VPAC1, and VPAC2, form a signaling axis that modulates both the innate and acquired immunity in several inflammatory/autoimmune diseases, including OA [ 20 , 21 ]. VIP sources in the joint comprise both nerve fibers of the sympathetic nervous system and a cellular origin, including lymphocytes and SF from OA and RA patients [ 20 , 21 , 22 ].…”

Vasoactive intestinal polypeptide plasma levels associated with affective symptoms and brain structure and function in healthy females

“…As accumulating evidence strengthens the association between depression and inflammation 10 , these findings are quite relevant considering that one of the main roles of VIP is the inhibition of proinflammatory mediators. The neuroprotective and anti-inflammatory properties of VIP are now being investigated for the treatment of neurodegenerative 65 , inflammatory, and autoimmune 66 diseases, and for use as a biomarker in specific conditions. Our findings provide important further evidence on psychological, functional, and structural levels to support VIP as a potential target for therapeutic investigation in anxiety and depression, and in disorders of the gut-brain axis with high psychological comorbidities.…”