VIP
Master Immunomodulatory Neuropeptide & Circadian Rhythm Regulator
VIP — Vasoactive Intestinal Peptide
VIP (Vasoactive Intestinal Peptide) is a 28-amino-acid neuropeptide that acts as a master anti-inflammatory signal throughout the nervous system, gut, and immune system. An inhaled form (Aviptadil) is FDA-approved for pulmonary hypertension.
VIP binds VPAC receptors on immune cells, suppressing the NF-kB inflammatory cascade and blocking production of TNF-alpha, IL-6, and other pro-inflammatory cytokines. It also promotes regulatory T-cells and regulates circadian rhythms.
Chronic inflammation drives autoimmune disease, cardiovascular disease, and neurodegeneration. VIP suppresses the NF-kB pathway while promoting immune tolerance — a uniquely powerful combination for inflammation research.
VIP is a pleiotropic neuropeptide with FDA approval (inhaled), Phase II/III clinical trial data for ARDS and COVID-19, and a well-characterized mechanism for suppressing chronic inflammation.
What is VIP?
VIP (Vasoactive Intestinal Peptide) is a 28-amino-acid neuropeptide produced throughout the nervous system, gut, and immune cells. It exerts potent anti-inflammatory effects by suppressing pro-inflammatory cytokines (TNF-alpha, IL-6, IL-12) and promoting regulatory T-cell differentiation. An inhaled form (Aviptadil) is FDA-approved for pulmonary hypertension.
- VIP (Vasoactive Intestinal Peptide) is a 28-amino acid neuropeptide found throughout the central and peripheral nervous system, gut, and immune system, acting on VPAC1 and VPAC2 receptors (G protein-coupled, cAMP-mediated).
- Primary physiological roles: smooth muscle relaxation (vasodilation, bronchodilation, gut motility regulation), neurotransmission in the autonomic nervous system, and potent immunomodulation (anti-inflammatory).
- VIP is one of the most potent endogenous anti-inflammatory peptides: it suppresses TNF-α, IL-6, IL-12, and IFN-γ production while promoting IL-10 and TGF-β, shifting immune responses toward Th2/regulatory phenotypes.
- The suprachiasmatic nucleus (SCN) — the brain's master circadian clock — uses VIP as its primary synchronizing signal between SCN neurons, making VIP central to circadian rhythm regulation.
- Research applications include studying autonomic nervous system function, gut motility, circadian biology, neuroinflammation, and the therapeutic potential of VIP receptor agonism in inflammatory and autoimmune conditions.
Molecular Composition
VIP is a 28-amino-acid neuropeptide (3,326.8 Da) belonging to the secretin/glucagon superfamily. It is produced by neurons in the enteric nervous system, hypothalamus, and throughout the peripheral nervous system, as well as by immune cells including T-cells and mast cells.
How Does It Work?
VIP suppresses chronic inflammation by activating VPAC receptors that inhibit NF-kB signaling, simultaneously promoting regulatory T-cell differentiation and vasodilation.
VIP binds VPAC1 and VPAC2 G-protein coupled receptors, activating adenylyl cyclase and elevating intracellular cAMP. This activates PKA, which phosphorylates and inhibits NF-kB — the master transcription factor for pro-inflammatory cytokine production. VIP also promotes Foxp3+ regulatory T-cell differentiation and tolerogenic dendritic cell polarization.
Key Research Pathways
VPAC1/VPAC2 Receptor Signaling / cAMP Cascade
Binds VPAC1 and VPAC2 G-protein coupled receptors, activating adenylyl cyclase and elevating intracellular cAMP — the primary mechanism for its anti-inflammatory and immunomodulatory effects.
Pro-Inflammatory Cytokine Suppression
Inhibits NF-kB activation in macrophages and dendritic cells, suppressing TNF-alpha, IL-6, IL-12, and IFN-gamma production.
Regulatory T-Cell Induction
Promotes the differentiation of Foxp3+ regulatory T-cells (Tregs) and tolerogenic dendritic cells, shifting immune responses toward tolerance.
Key Findings from the Literature
- FDA-approved inhaled form (Aviptadil) for pulmonary arterial hypertension
- Phase II/III clinical trials for ARDS and critical COVID-19 (significant survival improvement)
- Suppresses TNF-alpha, IL-6, IL-12, and IFN-gamma through NF-kB inhibition
- Promotes Foxp3+ regulatory T-cell differentiation (immune tolerance)
- Key neurotransmitter in the suprachiasmatic nucleus (circadian rhythm regulation)
Important Research Context
Research References
Peer-reviewed literature supporting the research profile of VIP
The following peer-reviewed studies form the primary evidence base for VIP's research profile. All references are sourced from PubMed, NCBI, and peer-reviewed scientific journals. Published research is available through PubMed, NCBI, and peer-reviewed biomedical journals.
- 1.
Delgado M, Ganea D. Anti-inflammatory neuropeptides: a new class of endogenous immunoregulatory agents. Brain, Behavior, and Immunity. 2008.PMID: 18598752
Comprehensive review of VIP's immunomodulatory functions across innate and adaptive immune compartments.
- 2.
Delgado M, Pozo D, Ganea D. The significance of vasoactive intestinal peptide in immunomodulation. Pharmacological Reviews. 2004.PMID: 15169929
VIP inhibits pro-inflammatory mediator production through VPAC receptor signaling, supporting its role in immune regulation.
- 3.
Gonzalez-Rey E, et al. Vasoactive intestinal peptide generates human tolerogenic dendritic cells that induce CD4 and CD8 regulatory T cells. Blood. 2006.PMID: 16397128
VIP induces tolerogenic dendritic cells and regulatory T cells, supporting anti-inflammatory research applications.
- 4.
Gonzalez-Rey E, Chorny A, Delgado M. Regulation of immune tolerance by anti-inflammatory neuropeptides. Nature Reviews Immunology. 2007.PMID: 17186031
Comprehensive review of VIP's role in immune regulation, neuroprotection, and inflammatory signaling.
VIP
Immune Research
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Technical Specifications
| Peptide Class | Neuropeptide/immunomodulator (28 amino acids) |
| Molecular Weight | 3,326.8 Da |
| Regulatory Status | FDA-approved inhaled (pulmonary hypertension); research chemical (injectable) |
| Available Sizes | 2mg, 5mg vials |
| Form | Lyophilized powder |
| Purity | ≥99% (third-party tested) |
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Other Compounds in This Guide
Supporting Research
VIP (Aviptadil) has a real clinical research history including Phase 2/3 trials for ARDS and COVID-19. Results have been mixed — some positive signals in small studies but larger trials have not consistently confirmed efficacy. VIP is not approved for any marketed indication.
References
- Delgado M, Ganea D.REVIEWAmino Acids. 2013. PubMedComprehensive review of VIP's role in immune regulation, neuroprotection, and inflammatory signaling; preclinical basis for clinical development.
Research Databases
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