Vasoactive intestinal peptide
Also known as: Aviptadil, PHI-27, RLF-100, Vasoactive intestinal polypeptide, VIP
Source Vasoactive intestinal peptide at Peptiology
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Summary
Vasoactive intestinal peptide (VIP) is a 28‑amino‑acid neuropeptide that acts as a neurotransmitter, vasodilator, and immunomodulator. It is studied for its roles in allergic inflammation, sleep regulation, skin microcirculation, and cancer biology, and is the hallmark secretory product of rare VIP‑producing neuroendocrine tumors (VIPomas). Research use includes inhaled, intravenous, or subcutaneous administration in experimental settings.
Mechanism of Action
VIP binds G‑protein‑coupled receptors VPAC1, VPAC2, and PAC1 on neurons, immune cells, and vascular endothelium. Receptor activation stimulates adenylate cyclase, raising intracellular cAMP and promoting smooth‑muscle relaxation, vasodilation, and secretion of anti‑inflammatory cytokines. In immune contexts, VIP modulates mast cells, ILC2s, and eosinophils, contributing to neurogenic inflammation. In cancer cells, VIP signaling can trans‑activate epidermal growth factor receptors, influencing proliferation and secretion of autocrine growth factors such as bombesin‑like peptides.
What the Research Shows
A 2023 review highlighted VIP’s contribution to neuroimmune communication in allergic rhinitis, where its release from nerves or immune cells can drive type‑2 inflammation and nasal hyperresponsiveness. Reviews from 2016 and 2018 described over‑expression of VPAC receptors on breast, lung, prostate, CNS, and neuroblastoma tumors, noting VIP‑mediated growth effects and the potential to use VIP analogues for tumor imaging or targeted drug delivery. A 2009 chapter reported VIP’s sleep‑inducing properties alongside other neuropeptides. A 2020 physiology article detailed VIP’s role in sympathetic cholinergic vasodilation of cutaneous microcirculation. An Endotext entry described VIPoma, a neuroendocrine tumor that secretes excess VIP, causing watery diarrhea, hypokalemia, and achlorhydria, with treatment focusing on fluid correction and somatostatin analogues rather than VIP itself. Across these sources, evidence is largely pre‑clinical or based on mechanistic reviews; no large‑scale clinical trials of VIP as a therapy are reported.
Reported Benefits
Experimental data suggest VIP may attenuate allergic inflammation by modulating neuroimmune pathways, support vasodilation and microvascular blood flow, and possess sleep‑promoting activity. In oncology, the high expression of VPAC receptors on several tumor types offers a theoretical avenue for imaging or delivering cytotoxic agents via VIP‑based conjugates. For VIPoma patients, recognizing the peptide’s excess production guides diagnosis and informs the use of somatostatin analogues to counteract symptoms.
Limitations of the Evidence
The literature consists mainly of reviews and mechanistic studies; there are no randomized clinical trials confirming therapeutic efficacy of VIP itself. Its pro‑growth effects in some cancers raise safety concerns for systemic use. Data on optimal dosing, long‑term outcomes, and comparative effectiveness are lacking, and the peptide remains investigational with no regulatory approval for any indication.
Safety Considerations
Direct safety data for administered VIP are not provided in the cited abstracts. As a potent vasodilator, systemic exposure could cause hypotension or flushing. In tumor contexts, VIP signaling may promote proliferation, suggesting a risk of tumor growth stimulation. The absence of human safety trials means adverse‑event profiles are uncertain, and use should be confined to controlled research settings.
How It Is Administered
Research formulations of VIP have been delivered by inhalation, intravenous infusion, or subcutaneous injection, reflecting its peptide nature and short plasma half‑life. Preparations are typically sterile aqueous solutions administered under experimental protocols.
Routes of Administration
Goals & Uses
- Erectile dysfunctionSexual HealthModerate
- Immunomodulation / autoimmune diseaseImmunologyLow
- Sjogren's syndromeAutoimmuneLow
- Acute Respiratory Distress Syndrome (ARDS)RespiratoryModerate
- COVID‑19 ARDSRespiratoryLow
- Inflammatory bowel diseaseGastroenterologyLow
- Pulmonary hypertensionCardiovascularModerate
- Bronchospasm / asthmaPulmonaryLow
- Pulmonary arterial hypertensionCardiovascular / PulmonaryModerate
Contraindications
- Known hypersensitivity to peptide formulationsAllergyModerate
- Known hypersensitivity to VIP or excipientsAllergyHigh
- VIPoma / known VIP-secreting tumorOncology / EndocrinologyModerate
- Severe hypotensionCardiovascularHigh
Adverse Effects
- Nausea / gastrointestinal discomfortGastrointestinalUncommon
- Facial flushingCardiovascular/DermatologicCommon
- Injection site reactionsLocalCommon
- HeadacheNeurologicUncommonPain in the head or upper neck
- HypotensionCardiovascularCommonLow blood pressure
- FlushingVascularCommonWarmth and redness of the skin
- TachycardiaCardiovascularCommonAbnormally fast heart rate
- Bronchospasm (paradoxical, inhalation route)PulmonaryRare
- DiarrheaGastrointestinalUncommonLoose or frequent stools
Drug Interactions
- Antihypertensive agentsModerate
- Beta‑blockersLow
- Other vasodilators (e.g., nitroglycerin)Moderate
- Beta-blockersLow
- Phosphodiesterase-5 inhibitors (e.g., sildenafil)Moderate
Population Constraints
- PregnancyReproductive SafetyRelative
- Pediatric patientsAgeRelative
- Elderly patientsAgeRelative
- Pregnant womenReproductiveRelative
- Renal or hepatic impairmentOrgan DysfunctionRelative
Regulatory Status
- European UnionInvestigationalClinical trials ongoing; not authorized for marketing.
- United StatesInvestigationalInvestigational New Drug (IND) applications filed; no approved product.
- United KingdomInvestigationalNo MHRA-approved indication. Under investigation in clinical trials.
No FDA‑approved product; studied as investigational therapeutic (e.g., Aviptadil) for pulmonary hypertension, ARDS, and inflammatory diseases.
Evidence & Sources
- Journal ArticleModerateZhou Y, et al.2023-01-01T00:00:00.000000Z
- Journal ArticleModerateMoody TW, Nuche-Berenguer B, Jensen RT2016-01-01T00:00:00.000000Z
- Journal ArticleModerateGarcía-García F, et al.2009-01-01T00:00:00.000000Z
- Journal ArticleModerateMoody TW, Ramos-Alvarez I, Jensen RT2018-01-01T00:00:00.000000Z
- Journal ArticleModerateFeingold KR, et al.2000-01-01T00:00:00.000000Z
- Journal ArticleModerateCracowski JL, Roustit M2020-01-01T00:00:00.000000Z
Frequently Asked Questions
What conditions is VIP being investigated for?
VIP is studied for its role in allergic rhinitis inflammation, sleep regulation, cutaneous blood flow, and as a targeting ligand for imaging or drug delivery in cancers that over‑express VPAC receptors. It is also a biomarker in VIP‑producing neuroendocrine tumors (VIPomas).
Has VIP been approved as a medication?
No. All current information places VIP in the research stage; there are no regulatory approvals for therapeutic use in any disease.
Can VIP be used to treat VIPoma?
Treatment of VIPoma focuses on correcting fluid loss and using somatostatin analogues to suppress VIP secretion. VIP itself is not used as a therapy; its excess production is the target of other agents.
What are the main safety concerns with VIP?
Potential vasodilatory effects leading to low blood pressure, flushing, and the theoretical risk of stimulating tumor growth in cancers that respond to VIP signaling. Human safety data are limited, so caution is advised in research settings.
How is VIP administered in experimental studies?
In research, VIP is typically given as a sterile peptide solution by inhalation, intravenous infusion, or subcutaneous injection, depending on the study design and target tissue.
What is Vasoactive intestinal peptide?
Vasoactive intestinal peptide (VIP) is a 28‑amino‑acid neuropeptide that acts as a neurotransmitter, vasodilator, and immunomodulator. It is studied for its roles in allergic inflammation, sleep regulation, skin microcirculation, and cancer biology, and is the hallmark secretory product of rare VIP‑producing neuroendocrine tumors (VIPomas). Research use includes inhaled, intravenous, or subcutaneous administration in experimental settings.
What is Vasoactive intestinal peptide used for?
Vasoactive intestinal peptide is educationally associated with: Erectile dysfunction, Immunomodulation / autoimmune disease, Sjogren's syndrome, Acute Respiratory Distress Syndrome (ARDS), COVID‑19 ARDS, Inflammatory bowel disease, Pulmonary hypertension, Bronchospasm / asthma, Pulmonary arterial hypertension. Educational only — not medical advice.
How is Vasoactive intestinal peptide administered?
Recorded routes of administration: Inhalation, Intranasal, Intravenous, Subcutaneous.
What are the potential side effects of Vasoactive intestinal peptide?
Reported adverse effects include: Nausea / gastrointestinal discomfort, Facial flushing, Injection site reactions, Headache, Hypotension, Flushing, Tachycardia, Bronchospasm (paradoxical, inhalation route), Diarrhea. This list is not exhaustive — consult a qualified clinician.
Who should avoid Vasoactive intestinal peptide?
Recorded contraindications: Known hypersensitivity to peptide formulations, Known hypersensitivity to VIP or excipients, VIPoma / known VIP-secreting tumor, Severe hypotension. Consult a qualified clinician before use.