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Peptide

Vasoactive Intestinal Peptide (VIP/Aviptadil)

VIP is a 28-amino acid neuropeptide with potent immunomodulatory, anti-inflammatory, and vasodilatory properties. Aviptadil is the synthetic form (RLF-100). FDA orphan drug designation for pulmonary conditions. Preclinical: Highly effective in arthritis, IBD, and autoimmune models. Clinical trials for pulmonary hypertension showed hemodynamic improvements. COVID-19 ARDS trials showed mixed results - improved survival in small trial but negative in larger TESICO trial (n=461). Major limitation: short plasma half-life requiring specialized delivery.

Research notice. This page is for education and research. Peptides may not be FDA-approved for human use and may only be legally available for research. Talk to a qualified clinician before considering any peptide.

Best evidence
Grade A
Conditions studied
4
Outcomes
9
Graded outcomes
1152

Evidence by condition

  • Strong
  • Moderate
  • Limited
  • Very limited

4 conditions, plus general outcomes

Acute Respiratory Distress Syndrome

Acute Respiratory Distress Syndrome: outcomes studied for Vasoactive Intestinal Peptide (VIP/Aviptadil)
GradeOutcomeEffectSizeStudiesPeopleStudies list
ARDS/Respiratory Failure

Mixed results: Small RCT (n=196) showed improved 60-day survival with IV aviptadil vs placebo. Larger TESICO trial (n=461) found no difference in primary endpoint (alive and free from respiratory failure at day 60). Clinical benefit uncertain.

NoneNo effect8 studies

Studies that measured ards/respiratory failure

Pulmonary Hypertension

Pulmonary Hypertension: outcomes studied for Vasoactive Intestinal Peptide (VIP/Aviptadil)
GradeOutcomeEffectSizeStudiesPeopleStudies list
Pulmonary Hemodynamics

Petkov 2003: Inhaled VIP reduced pulmonary artery pressure, improved cardiac output and mixed venous oxygen in PAH patients. VIP deficiency found in PAH patient serum and lung tissue. Small clinical studies show promise.

Improves (the measure goes up)Moderate effect7 studies

Studies that measured pulmonary hemodynamics

General

  • Immune Function: improves
  • Anti-Cancer Activity: improves
  • Liver Protection: improves
General: outcomes studied for Vasoactive Intestinal Peptide (VIP/Aviptadil)
GradeOutcomeEffectSizeStudiesPeopleStudies list
Immune Function

12 preclinical studies support this finding. Primarily preclinical evidence.

Improves (the measure goes up)Moderate effect11 studies

Studies that measured immune function

and 1 more in the citations list

Anti-Cancer Activity

5 preclinical studies support this finding. Primarily preclinical evidence.

Improves (the measure goes up)Small effect5 studies

Studies that measured anti-cancer activity

Liver Protection

4 preclinical studies support this finding. Primarily preclinical evidence.

Improves (the measure goes up)Small effect4 studies

Studies that measured liver protection

Reproductive Outcomes

2 preclinical studies support this finding. Primarily preclinical evidence.

Improves (the measure goes up)Small effect2 studies

Studies that measured reproductive outcomes

Cardiac Protection

2 preclinical studies support this finding. Primarily preclinical evidence.

Improves (the measure goes up)Small effect2 studies

Studies that measured cardiac protection

Rheumatoid Arthritis (RA)

  • Arthritis Severity Reduction: improves
Rheumatoid Arthritis (RA): outcomes studied for Vasoactive Intestinal Peptide (VIP/Aviptadil)
GradeOutcomeEffectSizeStudiesPeopleStudies list
Arthritis Severity Reduction

Preclinical: Completely abrogated joint swelling and cartilage/bone destruction in collagen-induced arthritis models. Protected against bone destruction. Downregulated both inflammatory and autoimmune disease components. No completed human RCTs.

Improves (the measure goes down)Large effect6 studies

Studies that measured arthritis severity reduction

Inflammatory Bowel Disease (IBD)

  • Inflammatory Bowel Disease: improves
Inflammatory Bowel Disease (IBD): outcomes studied for Vasoactive Intestinal Peptide (VIP/Aviptadil)
GradeOutcomeEffectSizeStudiesPeopleStudies list
Inflammatory Bowel Disease

Preclinical: VIP levels downregulated during intestinal inflammation. Animal models show potent anti-inflammatory effects. Nanomedicine delivery systems (SSM) allow lower effective doses. No completed human RCTs for IBD.

Improves (the measure goes down)Moderate effect3 studies

Studies that measured inflammatory bowel disease

Key findings

  • ARDS/Respiratory FailureAcute Respiratory Distress Syndrome
  • Pulmonary HemodynamicsPulmonary HypertensionImproves (the measure goes up)
  • Immune FunctionImproves (the measure goes up)

Studies cited

53 studies from PubMed

  1. Aviptadil Therapy in Acute Respiratory Distress Syndrome Patients: A Systematic Review and Meta-analysis.Indian journal of critical care medicine : peer-reviewed, official publication of Indian Society of Critical Care Medicine, 2025 · PMID 41368449
  2. Aviptadil as a Promising Intervention: A Case Study for Transfusion-Related Acute Lung Injury Treatment in a Cardiac Patient.Journal of cardiothoracic and vascular anesthesia, 2024 · PMID 38458826
  3. Vasoactive Intestinal Polypeptide for Patients Hospitalized With COVID-19 and Hypoxemic Respiratory Failure: Effect on Mortality-The TESICO TrialCrit Care Med, 2023 · PMID 37328169
  4. Vasoactive intestinal peptide blockade suppresses tumor growth by regulating macrophage polarization and function in CT26 tumor-bearing mice.Scientific reports, 2023 · PMID 36650220
  5. Intravenous aviptadil and remdesivir for treatment of COVID-19-associated hypoxaemic respiratory failure in the USA (TESICO): a randomised, placebo-controlled trial.The Lancet. Respiratory medicine, 2023 · PMID 37348524
  6. The Use of IV Vasoactive Intestinal Peptide (Aviptadil) in Patients With Critical COVID-19 Respiratory Failure: Results of a 60-Day Randomized Controlled TrialCrit Care Med, 2022 · PMID 36193478
  7. Brief Report: Rapid Clinical Recovery From Critical Coronavirus Disease 2019 With Respiratory Failure in a Pregnant Patient Treated With IV Vasoactive Intestinal Peptide.Critical care explorations, 2022 · PMID 35018346
  8. The Use of IV Vasoactive Intestinal Peptide (Aviptadil) in Patients With Critical COVID-19 Respiratory Failure: Results of a 60-Day Randomized Controlled Trial.Critical care medicine, 2022 · PMID 36044317
  9. Editorial: GPCR in Inflammatory and Cancer Diseases.Frontiers in endocrinology, 2020 · PMID 33101216
  10. Vasoactive Intestinal Peptide Changes the Frequency and Force of Myocardial Contraction in Rats.Bulletin of experimental biology and medicine, 2020 · PMID 33098516
  11. A Clinical Approach for the Use of VIP Axis in Inflammatory and Autoimmune DiseasesInt J Mol Sci, 2019 · PMID 31861827
  12. Vasoactive intestinal peptide increases apoptosis of hepatocellular carcinoma by inhibiting the cAMP/Bcl-xL pathway.Cancer science, 2019 · PMID 30390393
  13. Erectile dysfunction: a global review of intracavernosal injectables.World journal of urology, 2019 · PMID 30895359
  14. Why drugs fail in clinical trials in pulmonary arterial hypertension, and strategies to succeed in the future.Pharmacology & therapeutics, 2016 · PMID 27133570
  15. Vasoactive Intestinal Peptide (VIP) Nanoparticles for Diagnostics and for Controlled and Targeted Drug Delivery.Advances in protein chemistry and structural biology, 2015 · PMID 25819279
  16. The neuropeptide vasoactive intestinal peptide: direct effects on immune cells and involvement in inflammatory and autoimmune diseases.Acta physiologica (Oxford, England), 2015 · PMID 25422088
  17. Vasoactive intestinal peptide in pulmonary arterial hypertension.American journal of respiratory and critical care medicine, 2012 · PMID 22467806
  18. Immunomodulation of innate immune responses by vasoactive intestinal peptide (VIP): its therapeutic potential in inflammatory diseaseClin Immunol, 2009 · PMID 19604262
  19. Genetic association of vasoactive intestinal peptide receptor with rheumatoid arthritis: altered expression and signal in immune cellsArthritis Rheum, 2008 · PMID 18383379
  20. Inhalation of vasoactive intestinal peptide in pulmonary hypertensionEur Respir J, 2008 · PMID 18978135
  21. Pulmonary arterial hypertension: on the way to a manageable disease.Current opinion in investigational drugs (London, England : 2000), 2008 · PMID 18729002
  22. Bioactive analogues and drug delivery systems of vasoactive intestinal peptide (VIP) for the treatment of asthma/COPD.Peptides, 2007 · PMID 17537541
  23. [Vasoactive intestinal peptide-producing tumor (ViPoma)].Nihon rinsho. Japanese journal of clinical medicine, 2006 · PMID 17022564
  24. Protective effect of vasoactive intestinal peptide on bone destruction in the collagen-induced arthritis model of rheumatoid arthritisArthritis Res Ther, 2005 · PMID 16207319
  25. Vasoactive intestinal peptide modulates proinflammatory mediator synthesis in osteoarthritic and rheumatoid synovial cellsRheumatology (Oxford), 2004 · PMID 14657510
  26. The significance of vasoactive intestinal peptide in immunomodulation.Pharmacological reviews, 2004 · PMID 15169929
  27. Vasoactive intestinal peptide as a new drug for treatment of primary pulmonary hypertensionJ Clin Invest, 2003 · PMID 12684393
  28. Vasoactive intestinal peptide as a new drug for treatment of primary pulmonary hypertension.The Journal of clinical investigation, 2003 · PMID 12727925
  29. Vasoactive intestinal peptide in the immune system: potential therapeutic role in inflammatory and autoimmune diseases.Journal of molecular medicine (Berlin, Germany), 2002 · PMID 11862320
  30. Immunoeffector and immunoregulatory activities of vasoactive intestinal peptide.Regulatory peptides, 2002 · PMID 12409234
  31. Vasoactive intestinal peptide prevents experimental arthritis by downregulating both autoimmune and inflammatory components of the diseaseNat Med, 2001 · PMID 11329057
  32. Immunobiology of vasoactive intestinal peptide (VIP).Immunology today, 2000 · PMID 10637552
  33. Vasoactive intestinal peptide mediation of development and functions of T lymphocytes.Annals of the New York Academy of Sciences, 2000 · PMID 11193882
  34. Vasoactive intestinal peptide neurons as synaptic targets for vasopressin neurons in the suprachiasmatic nucleus. Double-label immunocytochemical demonstration in the rat.Neuroscience, 1999 · PMID 10363823
  35. Selectivity of effects of vasoactive intestinal peptide on macrophages and lymphocytes in compartmental immune responses.Annals of the New York Academy of Sciences, 1998 · PMID 9629281
  36. Expression of mRNA for vasoactive intestinal peptide in normal human colon and during inflammation.Molecular and cellular biochemistry, 1995 · PMID 7753037
  37. Oral sodium regulates extrahepatic metabolism of vasoactive intestinal peptide.Clinical science (London, England : 1979), 1991 · PMID 1649728
  38. Molecular characteristics of the cellular receptor for vasoactive intestinal peptide.Transactions of the Association of American Physicians, 1991 · PMID 1668991
  39. Vasoactive intestinal peptide. Messenger in a neuroimmune axis.Annals of the New York Academy of Sciences, 1990 · PMID 2165755
  40. Vasoactive intestinal peptide (VIP): an amnestic neuropeptide.Peptides, 1990 · PMID 2178250
  41. Vasoactive intestinal peptide (VIP), a putative neurotransmitter of nonadrenergic, noncholinergic (NANC) inhibitory innervation and its relevance to therapy.Journal of veterinary pharmacology and therapeutics, 1989 · PMID 2568497
  42. Vasoactive intestinal polypeptide and asthma.The New England journal of medicine, 1989 · PMID 2710206
  43. Vasoactive intestinal peptide and asthma.The New England journal of medicine, 1989 · PMID 2797074
  44. [Vasoactive intestinal peptide and substance P in the regulation of reproductive functions].Ceskoslovenska gynekologie, 1988 · PMID 2463108
  45. Vasoactive intestinal peptide as a mediator of intercellular communication in the cerebral cortex. Release, receptors, actions, and interactions with norepinephrine.Annals of the New York Academy of Sciences, 1988 · PMID 2839076
  46. Vasoactive intestinal peptide as a modulator of lymphocyte and immune function.Annals of the New York Academy of Sciences, 1988 · PMID 2839085
  47. The role of vasoactive intestinal peptide and other neuropeptides in the regulation of the immune response in vitro and in vivo.Annals of the New York Academy of Sciences, 1988 · PMID 3291699
  48. Vasoactive intestinal peptide secreting tumors. Pathophysiological and clinical correlations.Annals of the New York Academy of Sciences, 1988 · PMID 2839088
  49. Vasoactive intestinal peptide in the lung.Annals of the New York Academy of Sciences, 1988 · PMID 2898912
  50. Vasoactive intestinal peptide as a coronary vasodilator.Annals of the New York Academy of Sciences, 1988 · PMID 3291697
  51. Pulmonary clearance of vasoactive intestinal peptide.Thorax, 1986 · PMID 3010486
  52. Vasoactive peptides in the lung, with special reference to vasoactive intestinal peptide.Experimental lung research, 1982 · PMID 6762962
  53. Vasoactive intestinal peptide (VIP).Journal of clinical pathology. Supplement (Association of Clinical Pathologists), 1978 · PMID 298740