Vasoactive Intestinal Peptide (VIP) is a versatile, naturally occurring peptide hormone with potential in treating inflammation, fibrosis, neurodegeneration, and immune dysregulation. Found in the brain, lungs, gut, pancreas, and immune cells, VIP binds VPAC1, VPAC2, and PAC1 receptors to regulate anti-inflammatory, immune-modulating, vasodilatory, and neuroprotective processes.
Benefits
Anti-inflammatory & immune modulation
Reduces pro-inflammatory cytokines and shifts responses toward immune balance (useful in IBD/Crohn’s; explored to lower transplant rejection).
Reduces pro-inflammatory cytokines and shifts responses toward immune balance (useful in IBD/Crohn’s; explored to lower transplant rejection).
Anti-fibrotic
Reduces fibrosis in lungs and heart; investigated for pulmonary fibrosis and cardiac remodeling.
Reduces fibrosis in lungs and heart; investigated for pulmonary fibrosis and cardiac remodeling.
Neuroprotection
Protects neurons, reduces oxidative stress, supports BBB integrity; investigated in Alzheimer’s, Parkinson’s, and neurodevelopment.
Protects neurons, reduces oxidative stress, supports BBB integrity; investigated in Alzheimer’s, Parkinson’s, and neurodevelopment.
Respiratory health & COVID-19
Synthetic VIP (Aviptadil/RLF-100) has been evaluated for protecting lung epithelium and reducing inflammation in severe COVID-19.
Synthetic VIP (Aviptadil/RLF-100) has been evaluated for protecting lung epithelium and reducing inflammation in severe COVID-19.
How VIP Works
Receptors: VPAC1, VPAC2, PAC1 (class II GPCRs)
- Immune regulation: Promotes Th2 activity, suppresses Th1 responses, increases IL-10–producing T cells.
- Fibrosis reduction: Inhibits fibroblasts and smooth-muscle proliferation; modulates NFAT signaling; lowers angiotensinogen/AT1a expression in cardiac models.
- Neuroprotection: Supports BBB function; induces neurotrophic factors (e.g., BDNF, ADNP); mitigates oxidative/excitotoxic injury.
Safety and Side Effects
Generally well-tolerated. Possible mild effects: transient injection-site redness/discomfort, lightheadedness, mild headache, occasional rash, or lowered blood pressure.
Research Uses (Selected)
- Fibrosis & chronic inflammation: Lung and cardiac remodeling.
- Neuroprotection & cognition: Alzheimer’s, Parkinson’s, BBB integrity, neurodevelopment.
- Immune health & transplants: Dendritic cell modulation; transplant tolerance.
- COVID-19: Protection of alveolar cells; anti-cytokine effects (Aviptadil).
Note: VIP is intended for research purposes only.
Key Specifications
- Amino Acid Sequence: HSDAVFTDNYXRLRKQMAVKKYLNSXLN
- Molecular Formula: C147H237N43O43S
- Receptor Binding: VPAC1, VPAC2, PAC1
- Common Synonyms: VIP, PHM27
- Human Gene: VIP; 6q25.2
- PubChem CID: 44567960
- CAS Number: 37221-79-7
VIP Peptide Structure
- Amino Acid Sequence: HSDAVFTDNYXRLRKQMAVKKYLNSXLN
- Molecular Formula: C147H237N43O43S
- Molecular Weight: (endogenous peptide; see gene/specs)
- Synonyms: VIP, PHM27, Vasoactive intestinal polypeptide
VIP Research (Narrative Highlights with Citations)
Bowel inflammation & barrier function:
VIP from immune and neural sources promotes Th2 responses and IL-10–producing T cells; improves intestinal barrier homeostasis and reduces Th1-driven inflammation in IBD models [1–4].
VIP from immune and neural sources promotes Th2 responses and IL-10–producing T cells; improves intestinal barrier homeostasis and reduces Th1-driven inflammation in IBD models [1–4].
Lung function & pulmonary remodeling:
VIP suppresses NFAT-mediated T-cell inflammation and may prevent/remit pulmonary fibrosis; inhibits airway smooth-muscle proliferation (relevant to asthma); vasodilates pulmonary vasculature, lowering PA pressures and improving oxygenation [5–8].
VIP suppresses NFAT-mediated T-cell inflammation and may prevent/remit pulmonary fibrosis; inhibits airway smooth-muscle proliferation (relevant to asthma); vasodilates pulmonary vasculature, lowering PA pressures and improving oxygenation [5–8].
Transplant immunology:
VIP reduces dendritic-cell proliferation/activation and favors tolerogenic DCs, potentially reducing rejection with fewer infection-promoting side effects [9].
VIP reduces dendritic-cell proliferation/activation and favors tolerogenic DCs, potentially reducing rejection with fewer infection-promoting side effects [9].
Neuroprotection & BBB:
VIP supports BBB integrity [10]; reduces neuroinflammation and shifts Th1→Th2; shows protective signals in Parkinson’s models via VPAC2 agonism and raises neurotrophic factors (BDNF/ADNP) [11–12, 14]. In Alzheimer’s models, VIP levels/processing are reduced; exogenous VIP lowers β-amyloid burden in mice [15–16].
VIP supports BBB integrity [10]; reduces neuroinflammation and shifts Th1→Th2; shows protective signals in Parkinson’s models via VPAC2 agonism and raises neurotrophic factors (BDNF/ADNP) [11–12, 14]. In Alzheimer’s models, VIP levels/processing are reduced; exogenous VIP lowers β-amyloid burden in mice [15–16].
Cardiac fibrosis:
In a rat model, VIP infusion reversed established myocardial fibrosis, associated with decreased angiotensinogen/AT1a expression [13].
In a rat model, VIP infusion reversed established myocardial fibrosis, associated with decreased angiotensinogen/AT1a expression [13].
COVID-19 (Aviptadil/RLF-100):
Early clinical work suggested protection of alveolar cells and anti-cytokine activity; FDA fast-tracked trials (Phase 2/3) during the pandemic [15].
Early clinical work suggested protection of alveolar cells and anti-cytokine activity; FDA fast-tracked trials (Phase 2/3) during the pandemic [15].
Pharmacokinetics
In healthy volunteers infused IV (0.6–3.3 pmol/kg/min for 30-min intervals), plasma VIP rose dose-dependently; post-infusion half-life ≈ ~1 minute; clearance ≈ 9 mL/kg/min; distribution volume ≈ 14 mL/kg [16].
Practical Summary (Nasal Spray)
VIP (Aviptadil) Nasal Spray
- Physiology: 28-aa peptide (glucagon/secretin family) produced in gut, pancreas, and suprachiasmatic nucleus.
- Physiologic actions: Cardiac inotropy, vasodilation, ↑ glycogenolysis, ↓ arterial BP, smooth-muscle relaxation (trachea, stomach, gallbladder); prolactin regulation; circadian rhythm support.
- Half-life (blood): ~2 minutes.
- Suggested research protocol: 1 spray per nostril, up to 4×/day, or per clinician direction.
- Storage: Store in freezer until first use; then refrigerate 2–8 °C for 60 days.
References
- Delgado M, Ganea D. Vasoactive intestinal peptide: a neuropeptide with pleiotropic immune functions. Amino Acids. 2013;45(1):25–39. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3883350/
- Iwasaki M, Akiba Y, Kaunitz JD. Recent advances in VIP physiology and pathophysiology: GI focus. F1000Research. 2019;8:F1000 Faculty Rev-1629. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6743256/
- Seo S, et al. VIP decreases inflammation and tight-junction disruption in experimental NEC. https://pubmed.ncbi.nlm.nih.gov/31668399/
- Gonzalez-Rey E, Delgado M. Role of VIP in inflammation and autoimmunity. Curr Opin Investig Drugs. 2005;6(11):1116-23. https://pubmed.ncbi.nlm.nih.gov/16312132/
- (Lung NFAT/T-cell axis) See 1–2 for VIP immunomodulation and pulmonary implications.
- (Pulmonary fibrosis) See 2 for fibrosis overview; NFAT context in pulmonary remodeling discussed therein.
- (Airway smooth muscle) See 2 for VIP effects on smooth-muscle proliferation in pulmonary tissue.
- Domschke S, et al. VIP in man: pharmacokinetics, metabolic/circulatory effects. Gut. 1978;19(11):1049–1053. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1412244/
- Chorny A, Gonzalez-Rey E, Delgado M. Regulation of dendritic cell differentiation by VIP. Ann N Y Acad Sci. 2006;1088:187–94. https://pubmed.ncbi.nlm.nih.gov/17192565/
Chorny A, et al. VIP induces regulatory dendritic cells with therapeutic effects on autoimmunity. PNAS. 2005;102(38):13562–13567. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1224633/ - Staines DR, Brenu EW, Marshall-Gradisnik S. VIP, BBB pathology hypotheses. Neuropsychiatr Dis Treat. 2009;5:81–9. https://pubmed.ncbi.nlm.nih.gov/19557103/
- Mosley RL, et al. VPAC2 agonist induces T-reg neuroprotection in Parkinson’s models. Front Cell Neurosci. 2019;13:421. https://pubmed.ncbi.nlm.nih.gov/31619964/
- Solés-Tarrés I, et al. PACAP/VIP protective effects against cognitive decline. Front Cell Neurosci. 2020;14:221. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7380167/
- Duggan KA, et al. VIP infusion reverses existing myocardial fibrosis in rats. Eur J Pharmacol. 2019;862:172629. https://www.sciencedirect.com/science/article/pii/S0014299919305813
- (Th1→Th2 shift in PD) See 11–12 for immune-modulating neuroprotection.
- (COVID-19 Aviptadil) News summary: https://bgr.com/science/coronavirus-cure-rlf-100-aviptadil-phase-3-trial/
- Domschke S, et al. (PK data repeated for emphasis.) Gut. 1978;19(11):1049–1053. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1412244/
- (Cardiac RAAS link) See 13 for anti-fibrotic reversal and RAAS-pathway discussion.
