VIP

What It Is

Vasoactive Intestinal Peptide (VIP) is a 28-amino acid neuropeptide widely distributed throughout the central and peripheral nervous systems, gastrointestinal tract, and immune system. It functions as a neurotransmitter, neuromodulator, and potent vasodilator with broad anti-inflammatory and immunoregulatory properties. VIP signals through VPAC1 and VPAC2 receptors, which are coupled to adenylyl cyclase and activate the cAMP/PKA signaling cascade. In the lungs, VIP acts as a bronchodilator and pulmonary vasodilator, and VIP deficiency has been documented in patients with pulmonary arterial hypertension (PAH). Inhaled VIP has been studied in small clinical trials for PAH and showed improvements in pulmonary hemodynamics and exercise capacity. VIP's immunomodulatory effects are particularly notable — it suppresses pro-inflammatory cytokine production (TNF-α, IL-6, IL-12) while promoting regulatory T-cell differentiation, making it a candidate for autoimmune and inflammatory conditions. Research published in 2024–2025 has expanded investigation into VIP's neuroprotective effects, including its potential role in Parkinson's disease and neuroinflammation. VIP has a very short plasma half-life (approximately 1 minute), which limits its therapeutic utility without specialized delivery systems. It was returned to Category 1 compounding eligibility under the FDA's 2026 reclassification and is not FDA-approved as a drug product.

Why Researchers Study It

VIP is studied for its unique combination of vasodilatory, anti-inflammatory, and neuroprotective properties mediated through the VPAC receptor system. Its documented deficiency in pulmonary hypertension patients and its broad immunomodulatory effects make it relevant to multiple therapeutic areas. The challenge of its extremely short half-life has driven research into depot formulations, liposomal delivery, and longer-acting VIP analogs.

Proposed Mechanisms

• Binds PAC1 and VPAC receptors on immune cells and neurons
• Suppresses pro-inflammatory Th1/Th17 responses while preserving Treg function
• Restores normal circadian-immune coupling through VIP/PACAP signaling
• Modulates vagal tone and parasympathetic anti-inflammatory pathways
• Promotes angiogenesis and vasodilation via VIP receptor signaling

Evidence Snapshot

Commonly Discussed Benefits

Safety & Cautions

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Citations

1. [1] Delgado M. et al. — Vasoactive intestinal peptide: a neuropeptide with immunomodulatory function. Ann N Y Acad Sci. 2004 PubMed

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