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VIP (Vasoactive Intestinal Peptide): What the Research Actually Shows

Vasoactive intestinal peptide, called VIP, is a 28-amino-acid peptide that the body makes in nerves of the gut and brain and in some immune cells. It was isolated from the small intestine of the pig in 1970 and named for what it did to blood vessels in the first experiments (Said and Mutt, 1970).

Below is what the studies looked at, in what kind of model, and what they reported. This is a summary of published research, not a description of what the compound does in a person.

Quick facts

• Names: VIP, vasoactive intestinal peptide, vasoactive intestinal polypeptide. The synthetic form used in trials is called aviptadil.
• Sequence (pig and human VIP are identical): His-Ser-Asp-Ala-Val-Phe-Thr-Asp-Asn-Tyr-Thr-Arg-Leu-Arg-Lys-Gln-Met-Ala-Val-Lys-Lys-Tyr-Leu-Asn-Ser-Ile-Leu-Asn, 28 amino acids, with an amide group at the end (Carlquist et al., 1982, and UniProt P01282).
• Formula and weight: C147H238N44O42S, average molecular weight about 3326, calculated for the amidated peptide from the sequence above.
• Source: made in nerve endings of the gut and brain, and also by some immune cells (Gomariz et al., 2001).
• Family: it belongs to a superfamily of structurally related peptide hormones that includes glucagon, secretin and growth hormone-releasing hormone (Harmar et al., 2012).
• Receptors: VPAC1 and VPAC2, which also bind the related peptide PACAP. A third receptor, PAC1, is selective for PACAP.

What the research found

Results are listed as the authors reported them, in date order, and the limits come first where the authors stated them.

The discovery (Said and Mutt, Science, 1970). The authors isolated a 28-amino-acid peptide from pig small intestine and reported that it was chemically distinct from the kinins, substance P, glucagon and secretin. In animals, they reported that it caused widening of blood vessels, a fall in blood pressure, increased output from the heart, stimulation of breathing and a rise in blood sugar. Animal and chemistry work. PMID 5450698.

Found in the brain (Carlquist, Gastroenterology, 1982). The authors isolated VIP from pig brain and determined its sequence, which they reported was identical to the VIP already isolated from pig and cow intestine. This was the first time the peptide had been isolated from tissue outside the gut. Their amino acid analysis also matched VIP from human colon. Chemistry work. PMID 7084607.

How fast it leaves the blood (Domschke, Gut, 1978). Four healthy volunteers received VIP by infusion, and the authors measured plasma levels by radioimmunoassay. After each infusion ended, the level fell with an average half-time of about one minute. The authors wrote that the data do not support a role for VIP as a circulating hormone under normal conditions. Small human study with pharmacokinetic and physiological measurements, no clinical outcome. PMID 730072.

Macrophage and mouse endotoxin work (Delgado, Journal of Immunology, 1999). A Spanish group reported that VIP and the related peptide PACAP protected mice from a lethal dose of bacterial endotoxin, and that serum and peritoneal levels of the inflammatory signals TNF-alpha and IL-6 were lower in the treated mice. In a companion paper from the same group, the two peptides lowered the output of inducible nitric oxide synthase in cultured macrophages, working through the VPAC1 receptor. The authors described VIP and PACAP as “macrophage deactivating factors”. Cell and mouse work. PMIDs 9916753 and 10202009.

A mouse arthritis model (Delgado, Nature Medicine, 2001). The same group reported that giving VIP to mice in an experimental model of arthritis lowered how often the disease appeared and how severe it was, and that the treated mice had less joint swelling and less damage to cartilage and bone. They linked this to lower inflammatory and autoimmune activity in the animals. Mouse work from the group that published the 1999 papers. PMID 11329057.

Dendritic cells and T-cell types (Delgado, 2004). In two papers on cultured mouse dendritic cells, the group reported that VIP and PACAP acted in opposite directions on immature and on activated cells. On immature cells, they raised a surface marker and pushed T cells toward the Th2 type. On cells activated by endotoxin, they lowered the same markers and lowered T-cell stimulation. They also reported that VIP and PACAP lowered the Th1-attracting chemokine CXCL10 and raised the Th2-attracting chemokine CCL22, working through the VPAC1 receptor. Cell work. PMIDs 15020654 and 15231725.

A small inhaled-VIP study (Leuchte, European Respiratory Journal, 2008). Twenty patients with pulmonary hypertension inhaled a single dose of aviptadil during a heart catheter procedure. The authors reported a small and short-lived widening of the lung blood vessels and no change in systemic blood pressure, and wrote that further studies were needed. Single-dose, no control group, 20 people. PMID 18978135.

The largest randomized trial (Brown, Lancet Respiratory Medicine, 2023, TESICO). The trial compared intravenous aviptadil with matched placebo in hospitalized adults with COVID-19 respiratory failure at 28 US sites. The independent monitoring board recommended stopping the aviptadil comparison early for futility. Among 461 participants analyzed, the authors reported no difference in the primary outcome (odds ratio 1.11, 95% CI 0.80 to 1.55) and no difference in deaths by day 90 (38% with aviptadil, 36% with placebo). A smaller earlier trial of 196 patients reported higher survival at 60 days while missing its primary endpoint (Youssef et al., 2022). Randomized, placebo-controlled trial in a single condition. PMID 37348524.

How it works, as far as anyone knows

VIP is reported to act on cell-surface receptors of the class B family of G protein-coupled receptors. VPAC1 and VPAC2 bind it with high affinity, and they also bind PACAP, while PAC1 is selective for PACAP (Harmar et al., 2012). In the lab, binding to these receptors raises the cell messenger cAMP, and the Delgado group’s papers above found that route involved in their immune-cell results.

Reviews describe VIP as having a wide set of roles in the nervous system, the gut, the circulation and the immune system, and describe its immune role as modulating rather than only suppressing (Gomariz et al., 2001). That breadth is also a difficulty for research: the same peptide produces different results depending on the cell type, its activation state and the receptor present.

What the research does not establish

• Most of the findings are from cells in culture and from mice. They describe what happened in a research model, not what would happen in a person.
• The immune-cell and arthritis papers cited here share authors, and the mouse arthritis result is from the same group as the 1999 macrophage papers.
• VIP left plasma with a half-time of about one minute in the one volunteer study we found, and results with the natural peptide in animals may not carry over to a person (Domschke et al., 1978).
• The human studies we found are small, uncontrolled or about a single condition. The one large randomized trial reported no difference from placebo (Brown et al., 2023).
• The 2022 smaller trial was funded by the companies developing aviptadil, and several of its authors reported consulting or funding from them (Youssef et al., 2022).
• Nothing here is a safety conclusion, and this is not a claim that the compound is safe to use.

Common questions

What is VIP?

VIP, short for vasoactive intestinal peptide, is a 28-amino-acid neuropeptide first isolated from pig small intestine in 1970 and later found in the brain (Said and Mutt, 1970, Carlquist et al., 1982).

Is VIP a peptide?

Yes. It is a 28-amino-acid peptide and a member of a superfamily of structurally related peptide hormones (Harmar et al., 2012).

What does VIP bind to?

VIP binds two receptors called VPAC1 and VPAC2, which also bind the related peptide PACAP. A third receptor, PAC1, is selective for PACAP (Harmar et al., 2012).

Why do researchers study VIP in immune cells?

Immune cells both make VIP and carry its receptors, and lab studies in macrophages and dendritic cells reported that VIP changed how those cells behaved (Gomariz et al., 2001, Delgado et al., 1999). Those are results in cultured cells and mice.

Has VIP been studied in people?

Yes, in a small number of studies. A 1978 volunteer study measured how fast it leaves the blood, a 2008 study had 20 people inhale a single dose, and a 2023 randomized trial in hospitalized adults with COVID-19 respiratory failure reported no difference from placebo (Domschke et al., 1978, Leuchte et al., 2008, Brown et al., 2023).

Is VIP in the Etched Research shop?

No. VIP is not part of the Etched Research retail catalog. This page is in the research library because the compound is part of immune-signaling research, and the library covers more compounds than the shop does.

More in this research area: Immune System Research | Research Library

Last reviewed 2026-10-19.

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