28AA Clinical (Niche Indication)
VIP
An endogenous 28-amino-acid neuropeptide with potent anti-inflammatory and bronchodilatory effects; the final step in the Shoemaker CIRS protocol with a meaningful clinical record.
In Plain English:
VIP is a signalling peptide your nervous system naturally produces to calm inflammation, relax airways and blood vessels, and regulate immune responses. Scientists have studied it for over 50 years. In clinical practice it is best known as the capstone of the Shoemaker protocol for mould illness (CIRS)—where intranasal VIP is used to normalise brain volume loss and inflammatory markers after the upstream steps are complete. It is also being studied as inhaled aviptadil for pulmonary arterial hypertension, where it was granted FDA Orphan Drug and Breakthrough Therapy designations.
Research Maturity
Clinical (Niche Indication) (15,084 publications on PubMed as of May 2026 (search: "vasoactive intestinal peptide")+ Studies)
Focus
Immune Modulation
Neuroprotection
Vascular Tone & Pulmonary Function
Route
Inhaled
IV
Nasal
SubQ
Origin
Endogenous human neuropeptide first isolated from porcine small intestine in 1970 by Said and Mutt; produced by enteric neurons, peripheral autonomic nerves, lungs, and immune cells.
Mechanism
Binds VPAC1 and VPAC2 receptors (GPCRs) to stimulate adenylyl cyclase and raise intracellular cAMP, triggering: smooth-muscle relaxation (vasodilation, bronchodilation); inhibition of NF-κB and suppression of TNF-α, IL-6, IL-12, IFN-γ; upregulation of IL-10 and TGF-β; and promotion of T-regulatory cell differentiation. Rapidly degraded by DPP-4 and plasma endopeptidases (plasma t½ ~1–2 min), requiring frequent intranasal dosing or inhaled/IV delivery for sustained effect.
Outcome
Normalisation of CIRS biomarkers (TGF-β1, MMP-9, C4a, VEGF); restoration of grey matter nuclear volume on NeuroQuant MRI; reduction of mean pulmonary artery pressure and improved cardiac output in PAH; broad anti-inflammatory and immunomodulatory effects across neurological, gastrointestinal, and autoimmune models.
