VIP (Vasoactive Intestinal Peptide)

What Is VIP (Vasoactive Intestinal Peptide)?

VIP (vasoactive intestinal peptide) is a 28-amino-acid neuropeptide originally isolated from porcine intestine and a member of the secretin/glucagon/GHRH superfamily, the same backbone family as GLP-1 and GIP. It signals through two G-protein-coupled receptors, VPAC1 and VPAC2, both of which activate adenylyl cyclase, raising cAMP and activating PKA. VPAC1 is expressed on immune cells (T cells, macrophages, dendritic cells), epithelial tissue, and the gut lining, while VPAC2 dominates in the lungs, smooth muscle, and parts of the central nervous system.

The downstream effect of VIP binding is strongly anti-inflammatory: it suppresses TNF-alpha, IL-6, and IL-12, shifts T cells toward regulatory (Treg) phenotypes, calms macrophage activation, and dilates pulmonary and systemic vasculature. VIP is also a major regulator of the suprachiasmatic nucleus, the brain's circadian clock, which is why VIP deficiency is associated with sleep disruption and HPA-axis dysregulation in chronic illness models. The best-known clinical context is Ritchie Shoemaker's Chronic Inflammatory Response Syndrome (CIRS) framework for mould and biotoxin illness, where patients show depleted VIP alongside elevated TGF-beta1, MMP-9, C4a, and VEGF. The same anti-inflammatory mechanism is under study in pulmonary sarcoidosis, pulmonary arterial hypertension, and ARDS through the synthetic form aviptadil. Plasma half-life is one to two minutes, which is why the intranasal route dominates the research literature.