VIP (Vasoactive Intestinal Peptide)

How does VIP work?

VIP signals through the class-II G-protein-coupled receptors VPAC1 and VPAC2, generally raising intracellular cyclic AMP. From that single signaling axis flow several distinct physiological roles — vasodilation, smooth-muscle relaxation, immunomodulation, circadian regulation, and neuroprotection. The vasodilatory and smooth-muscle actions are well-established physiology; the immune and therapeutic effects are characterized largely in preclinical models.

1. VPAC1 / VPAC2 Receptor Agonism. VIP binds the class-II G-protein-coupled receptors VPAC1 and VPAC2, generally raising intracellular cyclic AMP (cAMP).
2. Vasodilation & Smooth-Muscle Relaxation. VIP is a potent vasodilator and relaxes gastrointestinal and airway smooth muscle.
3. Immunomodulation / Anti-Inflammatory [1][2][3]. VIP functions as a broad immunomodulator: it inhibits activation of macrophages, dendritic cells, and microglia while promoting Th2 and regulatory T-cell (Treg) responses. These immune effects are characterized largely in preclinical models.
4. Circadian Regulation. In the suprachiasmatic nucleus, VIP acts as a master regulator of circadian rhythm.
5. Neuroprotection. VIP is a neuroprotective neuropeptide.

What is VIP researched for?

VIP's research base is dominated by preclinical immunology, with the clinical work concentrated on the investigational synthetic form aviptadil. The peptide was first isolated from porcine small intestine by Said and Mutt in 1970. The findings below should be read as largely preclinical and mechanistic, except where an investigational clinical program is named.

1. Immunomodulation (Foundational Review) [1]. Delgado, Ganea, and colleagues characterized VIP's significance in immunomodulation (Pharmacol Rev), establishing its broad anti-inflammatory profile. Mechanistic/preclinical.
2. Immune-Cell Effects & Autoimmune Disease [2]. VIP exerts direct effects on immune cells and is implicated in inflammatory and autoimmune disease models (Ganea et al. 2015).
3. Innate Immunity & Inflammatory Disease [3]. Reviews describe VIP's immunomodulation of innate immune responses and its proposed therapeutic potential in inflammatory disease (PMID 19604262). Largely preclinical.
4. Allergic Disease [4]. Neuroendocrine-cell-derived VIP has been studied in allergic diseases (Verma et al. 2017).
5. Aviptadil (Investigational, Negative Trial) [7]. Brown et al. 2023 (TESICO, part of ACTIV-3b, PMID 37348524) randomized 461 hospitalized adults with COVID-19 acute hypoxaemic respiratory failure to IV aviptadil (identical amino-acid sequence to VIP) or placebo. The trial was stopped early for futility: the primary 90-day outcome did not significantly favor aviptadil (OR 1.11, 95% CI 0.80-1.55, p=0.54), and 90-day mortality was not significantly different (38% vs 36%, p=0.78). This is a genuine human RCT of the VIP sequence itself, but a negative one — it did not yield FDA approval.

How is VIP dosed?

There is no validated research-use dose for VIP. Its synthetic form aviptadil has been dosed in investigational clinical trials, but those regimens are route-specific and remain investigational — not an approved standard.

Prof. Peptide reports what trials established and what research communities practice, labelled separately. Neither is a recommendation.

Aviptadil has been administered in investigational programs (for example, intravenous and inhaled routes in ARDS/COVID-19 trials), but those regimens are investigational and route-specific and are not reproduced here. For research-grade VIP, there is no established dose; it is unapproved material handled in the laboratory, and its very short plasma half-time (about one minute after IV infusion, Domschke 1978) [8] further complicates any extrapolation. Researchers reconstitute lyophilized powder with bacteriostatic or sterile water (see storage below); any volume chosen is a generic handling convenience, not a dosing recommendation. Prof. Peptide deliberately does not publish an injectable mg or mg/kg schedule for research-grade VIP — none has been validated.

What are the side effects of VIP?

The human safety of research-grade VIP is not established; it is unapproved, Research Use Only material and is not intended for human consumption, so nothing here should be read as human-use guidance. Pharmacologically, VIP's defining actions — potent vasodilation and relaxation of gastrointestinal and airway smooth muscle — predict effects such as flushing, lowered blood pressure, and loose stools; these are anticipated from the mechanism rather than quantified controlled-safety data for research material. For the investigational drug aviptadil, documented safety information resides in its clinical-trial records, not on this page.

How should VIP be stored?

1. Research-grade VIP (lyophilized powder): reported stored cold and desiccated, protected from light, frozen at -20°C for long-term storage; 2–8°C is acceptable short-term.
2. Bacteriostatic or sterile water for injection is reported used, added slowly down the inside wall of the vial with a gentle swirl rather than shaking.
3. Reconstituted solution: refrigerate at 2–8°C and keep protected from light. VIP has a very short plasma half-time in the body (about one minute after IV infusion, Domschke 1978) [8]; reconstituted material is usually handled promptly and kept cold.
4. VIP is stored protected from light at all times, in the original packaging.
5. Discard if the solution is cloudy, discolored, or contains particles.

What are the limitations of VIP research?

This is the most important section to read carefully. VIP is an endogenous human neuropeptide, not an approved drug, and the therapeutic case for it is earlier-stage than the marketing around it suggests.

VIP FAQ

References

1. Delgado M, Ganea D, et al. The significance of vasoactive intestinal peptide in immunomodulation. Pharmacol Rev. PMID 15169929. https://pubmed.ncbi.nlm.nih.gov/15169929/
2. Ganea D, Hooper KM, Kong W. The neuropeptide VIP: direct effects on immune cells and involvement in inflammatory and autoimmune diseases. Acta Physiol (Oxf). 2015;213(2):442-52. PMID 25422088. https://pubmed.ncbi.nlm.nih.gov/25422088/
3. Smalley SG, Barrow PA, Foster N, et al. Immunomodulation of innate immune responses by vasoactive intestinal peptide: its therapeutic potential in inflammatory disease. Clin Exp Immunol. 2009;157(2):225-34. PMID 19604262. https://pubmed.ncbi.nlm.nih.gov/19604262/
4. Verma AK, et al. Neuroendocrine-cell-derived VIP in allergic diseases. Cytokine Growth Factor Rev. 2017;38:37-48. PMID 28964637. https://pubmed.ncbi.nlm.nih.gov/28964637/
5. Said SI, Mutt V. Isolation of vasoactive intestinal peptide from porcine small intestine. 1970. (Foundational discovery; cited by name, no PubMed link added.)
6. Chemical identifiers: CAS 40077-57-4 (VIP peptide; human, porcine, and rat sequences are identical). (Cited by name/ID, no URL added.)
7. Brown SM, Barkauskas CE, Grund B, et al. Intravenous aviptadil and remdesivir for treatment of COVID-19-associated hypoxaemic respiratory failure in the USA (TESICO): a randomised, placebo-controlled trial. Lancet Respir Med. 2023;11(9):791-803. PMID 37348524. NCT04843761. https://pubmed.ncbi.nlm.nih.gov/37348524/
8. Domschke S, Domschke W, Bloom SR, et al. Vasoactive intestinal peptide in man: pharmacokinetics, metabolic and circulatory effects. Gut. 1978;19(11):1049-1053. PMID 730072. https://pubmed.ncbi.nlm.nih.gov/730072/

Published Studies