VIP

What Is VIP?

VIP is a naturally occurring 28-amino-acid peptide, first identified in the intestinal tract but now known to be produced widely throughout the body, including by nerve cells in the central and peripheral nervous system, endocrine cells, and immune cells like T and B lymphocytes. It belongs to the glucagon-secretin hormone family and acts as an inhibitory neurotransmitter, generally raising cyclic AMP levels in the cells it targets.

Its synthetic form, aviptadil, has a real clinical development history. It received FDA approval for human trials as early as 2001 and has been studied in controlled trials for pulmonary hypertension, where inhaled aviptadil produced measurable pulmonary vasodilation. More recently, it was studied as a treatment for COVID-19-related acute respiratory distress syndrome, receiving Fast Track Designation, though it was never approved for that or any other indication, and compounded VIP nasal spray products sold separately are not FDA-approved.

What VIP is Being Researched For?

• Pulmonary Hypertension

  Controlled trials of inhaled aviptadil in patients with pulmonary hypertension found it produced measurable, selective pulmonary vasodilation, the foundational human evidence behind VIP's clinical development.^[1]

• COVID-19-Related Lung Injury

  VIP's known anti-inflammatory and immune-modulating properties led to its evaluation as aviptadil in multiple controlled trials for COVID-19 ARDS, based on its established role in regulating the immune response and reducing SARS-CoV-2's ability to enter cells through downregulation of viral entry proteins.^[2]

• Immune Regulation Research

  Beyond specific clinical indications, VIP has been studied extensively for its broader role in immune homeostasis, including suppressing pro-inflammatory cytokine release and promoting regulatory T-cell activity, research that underlies its exploration across multiple inflammatory and autoimmune contexts.

How VIP Works

• Binding VPAC Receptors to Raise Cyclic AMP

  Research points to VIP binding two G-protein coupled receptors, VPAC1 and VPAC2, found on immune cells, blood vessels, and neurons, generally increasing intracellular cyclic AMP and triggering downstream anti-inflammatory and vasodilatory effects.^[1]

• Suppressing Inflammatory Signaling

  Research points to VIP inhibiting NF-kB activation and suppressing the release of pro-inflammatory cytokines, while promoting regulatory T-cell activity, a shift toward immune regulation rather than broad immune suppression.

• A Proposed Antiviral Mechanism in COVID-19 Research

  Research points to VIP downregulating ACE2 and TMPRSS2, two proteins the SARS-CoV-2 virus uses to enter cells, in laboratory models, reducing infection rates in cell-based experiments, a mechanism distinct from its established anti-inflammatory activity.^[2]

Reconstitution and Handling

VIP is typically supplied as a lyophilized powder in a sealed vial and reconstituted with bacteriostatic water before use in a research setting. Water should be added slowly rather than injected directly into the powder, and the vial should be swirled, not shaken.

Since the amount of water used affects the concentration of the final solution, researchers often use a dosage calculator to work this out before mixing. Keel Bio's calculator is a commonly used tool for this. Once reconstituted, the solution is kept refrigerated to help preserve its stability.

Key Takeaways

VIP stands out for having a naturally occurring role across the nervous, immune, and endocrine systems, combined with a genuine clinical trial history for its synthetic form, aviptadil, spanning pulmonary hypertension and COVID-19 research. Despite that real trial history, including Fast Track Designation during the pandemic, it has not achieved FDA approval for any indication, which is an important distinction from compounds like semaglutide or tirzepatide that completed the full approval process.

Frequently Asked Questions

Sources and Research

1. Leuchte HH, Baezner C, Baumgartner RA, et al. Inhalation of vasoactive intestinal peptide in pulmonary hypertension. Eur Respir J. 2008;32(5):1289-1294.
2. Youssef MEEA, et al. Anticipated pharmacological role of Aviptadil on COVID-19. Bull Natl Res Cent. 2021;45:200.