VIP (Vasoactive Intestinal Peptide)

Vasoactive Intestinal Peptide (VIP) is one of the most widely distributed and biologically influential regulatory peptides in the human body. First isolated in 1970, VIP is a 28–amino acid neuropeptide produced throughout the central nervous system, lungs, gastrointestinal tract, cardiovascular system, and immune tissues. Despite its name suggesting it only affects the intestines, VIP has widespread effects on blood vessels, the immune system, circadian rhythms, and multiple organ systems. Your body naturally produces VIP, and it plays a crucial role in regulating inflammation, blood vessel dilation, smooth muscle relaxation, and communication between the nervous and immune systems. VIP is part of what scientists call the third branch of the autonomic nervous system, distinct from both the sympathetic (fight-or-flight) and parasympathetic (rest-and-digest) systems. VIP has gained significant attention in functional medicine for its role in treating Chronic Inflammatory Response Syndrome (CIRS), a complex multi-system illness often triggered by exposure to water-damaged buildings and mold. Dr. Ritchie Shoemaker pioneered the use of VIP nasal spray as the final step in his CIRS treatment protocol, documenting its effects in over 10,000 patients. VIP deficiency has been found in over 98% of patients with CIRS. Rather than acting as a single-target peptide, VIP functions as a global regulator—influencing vascular tone, immune signaling, autonomic balance, gut function, hormone regulation, and circadian rhythm coordination. It has been found in both free and bound forms in the hypothalamus, limbic system, pituitary, gut, and pancreas, where it co-localizes with hormones including ACTH, MSH, TSH, and glucagon.

Key Characteristics

• Length: 28 amino acids
• Classification: Endogenous neuropeptide, regulatory peptide
• Discovery: 1970
• Receptors: VPAC1 and VPAC2 (G-protein-coupled receptors)
• Distribution: CNS, lungs, GI tract, cardiovascular system, immune tissues, pancreas,

pituitary

• Pharmaceutical form: Aviptadil (synthetic VIP)
• Primary signaling: cAMP-mediated via adenylate cyclase activation
• Administration: Nasal spray (standard), inhaled, IV (clinical studies)

How It Works

VIP acts through G-protein-coupled receptors (VPAC1 and VPAC2) expressed across multiple organs and cell types, including smooth muscle cells, immune cells, epithelial tissues, and neurons. When VIP binds to these receptors, it activates adenylate cyclase, which increases cyclic AMP (cAMP) inside cells. This leads to activation of protein kinase A and CREB (cAMP Response Element-Binding protein), which influence gene expression and cellular behavior.

Anti-Inflammatory and Immune Regulation

One of VIP’s most extensively studied roles is immune regulation. VIP reduces production of pro-inflammatory cytokines (TNF-α, IL-1, IL-6, IL-12) while increasing production of anti- inflammatory cytokines (IL-4, IL-10, IL-13) and insulin-like growth factor 1 (IGF-1). It downregulates Th17 immune responses associated with autoimmunity and promotes development of regulatory T cells (Tregs) that help control inflammation. Rather than simply suppressing immunity, VIP helps restore immune equilibrium—shifting signaling away from excessive inflammation toward immune tolerance. VIP functions as a macrophage deactivating factor, stopping the production of pro-inflammatory cytokines from these key immune cells. Research has also demonstrated that VIP regulates the Th17/Treg pathway, making it an attractive candidate for autoimmune conditions.

Vascular Effects and Vasodilation

VIP is a potent endogenous vasodilator. It causes vasodilation by relaxing smooth muscle in blood vessel walls, reduces pulmonary artery pressure, improves blood flow to tissues, and stimulates VEGF (vascular endothelial growth factor) for new blood vessel formation. Because vascular tone influences oxygen delivery, metabolic efficiency, and neurological function, VIP’s vascular effects may help explain improvements in circulation, exercise tolerance, and cognitive clarity.

Pulmonary and Respiratory Function

VIP relaxes airway smooth muscle, providing bronchodilation. It has been studied in human models of pulmonary arterial hypertension (PAH), COPD, and inflammatory lung disease. Inhaled or infused VIP has demonstrated temporary pulmonary vasodilation, improved oxygenation, and modest improvements in exercise tolerance. Research using VIP gene knockout models has demonstrated that VIP deficiency leads to both pulmonary vascular remodeling and inflammation, mediated through uncontrolled calcineurin-NFAT signaling.

Neuroendocrine Regulation

VIP regulates circadian rhythms through actions in the suprachiasmatic nucleus (SCN), the brain’s master clock. It influences hormone release from the pituitary, including growth hormone, prolactin, and luteinizing hormone. VIP regulates insulin and glucagon release from the pancreas and acts as a neurotransmitter in the brain, affecting cognition and mood. Research in healthy females demonstrated associations between plasma VIP levels and brain volume and functional connectivity in regions associated with anxiety and depression.

Gastrointestinal Function

VIP plays a critical role in gastrointestinal motility, secretion, and barrier integrity. It promotes intestinal epithelial cell health through differentiation, proliferation, and cell adhesion. VIP regulates stomach acid secretion, controls water and ion absorption in the colon, supports gut barrier integrity, and has antimicrobial properties against certain pathogens. It aids proper peristalsis by inhibiting smooth muscle contraction and triggering mucus secretion by goblet cells. Loss or dysregulation of VIP signaling has been associated with inflammatory bowel disease patterns.

Neuroprotective Effects

VIP has demonstrated neuroprotective properties, including restoration of gray matter volume in brain regions affected by CIRS, support for neuroplasticity, and potential protection against neurodegeneration. Studies suggest VIP and associated molecules are important regulators of neurodevelopment and strong candidates for therapeutic development in neurological disorders linked to neuroinflammation.

Cardiovascular Regulation

VIP is important in regulating coronary blood flow, cardiac contraction, and heart rate. The amount of VIP in the heart decreases as fibrosis progresses, and VIP becomes undetectable in end-stage cardiomyopathy, suggesting a protective role in cardiac function.

Benefits

CIRS and Mold Illness

• Reduction in inflammatory markers (C4a, TGF-beta 1, MMP9)
• Normalization of hormone levels (testosterone, estradiol, Vitamin D)
• Improvement in pulmonary artery pressure
• Correction of gray matter nuclear atrophy in the brain
• Reduction in symptoms (fatigue, cognitive dysfunction, pain)
• Normalization of clotting abnormalities, including acquired von Willebrand’s
• Correction of VEGF levels
• 100% of patients showed quality-of-life improvement in Shoemaker’s published studies

Inflammatory and Autoimmune Conditions

• Rheumatoid arthritis: reduced joint inflammation and destruction in animal models
• Pulmonary arterial hypertension: inhaled VIP reduced pulmonary artery pressure
• Sarcoidosis: improved symptoms and reduced TNF-α production with inhaled VIP
• Inflammatory bowel disease: maintained intestinal barrier function
• Potential in multiple sclerosis, Sjögren’s syndrome, type 1 diabetes, and uveoretinitis

Pulmonary and Respiratory Health

• Bronchodilation and airway smooth muscle relaxation
• Reduction of pulmonary artery pressure
• Improved oxygenation and exercise tolerance
• Anti-inflammatory and anti-proliferative effects in lung tissue

Brain Health and Cognition

• Restoration of gray matter volume in CIRS-affected brain regions
• Support for neuroplasticity and neurodevelopment
• Circadian rhythm regulation through the suprachiasmatic nucleus
• Associations with lower anxiety and improved mood stability

Gut Health

• Intestinal epithelial cell health and barrier integrity
• Regulation of stomach acid secretion and colonic absorption
• Antimicrobial properties against certain pathogens
• Proper peristalsis and mucus secretion support

Hormone Regulation

• Supports testosterone and estrogen production
• Regulates growth hormone, prolactin, and LH release
• Influences insulin and glucagon release from the pancreas
• Normalizes hormones disrupted by chronic inflammation

Multiple Chemical Sensitivity

• Low VIP correlates with chemical sensitivity
• Restoring VIP levels associated with decreased chemical reactions in CIRS patients

Cardiovascular Support

• Increases coronary and peripheral blood flow
• Reduces vascular resistance
• Supports endothelial function
• Stimulates VEGF for vascular repair

What the Science Shows

CIRS Treatment Study (Shoemaker et al., 2013) This published open-label study examined VIP nasal spray in 20 patients with refractory CIRS from water-damaged building exposure. Patients received 50 mcg VIP nasal spray four times daily for at least 18 months. Results showed significant reduction in symptoms and inflammatory markers (C4a, TGF-beta 1, MMP9), improvement in pulmonary function and exercise tolerance, normalization of hormone levels (estradiol, testosterone), and improvement in quality of life in 100% of patients. No significant adverse events were reported. Over 300 physicians have since prescribed intranasal VIP for CIRS patients, with over 90% reporting symptom reduction and inflammatory marker improvement.

RNA Sequencing Study (Ryan and Shoemaker, 2016) RNA sequencing on CIRS patients treated with VIP documented changes in gene expression, showing a shift away from inflammatory gene profiles and improvement in metabolic pathways. The study confirmed the molecular basis for clinical improvements, demonstrating that VIP treatment induces a shift in both metabolic state and innate immune functions that coincide with clinical healing.

Brain MRI Study (Shoemaker et al., 2017) An MRI study documented restoration of gray matter nuclear volume in CIRS patients treated with intranasal VIP. Patients served as their own controls (before and after VIP). Multiple brain regions showed improvement, and changes correlated with clinical symptom improvement. The study demonstrated both safety and durability of benefit, with no significant adverse effects.

Pulmonary Arterial Hypertension Study (Petkov et al., 2003) A study published in the Journal of Clinical Investigation examined inhaled VIP for primary pulmonary hypertension. VIP was described as a potent systemic and pulmonary vasodilator that resulted in substantial improvement of hemodynamic and prognostic parameters without side effects. Separate research using VIP gene knockout models proposed that VIP acts as an endogenous modulator of pulmonary vascular remodeling and inflammation through suppression of NFAT activation.

Sarcoidosis Study (Prasse et al., 2010) In an open clinical Phase II study, 20 patients with histologically proven sarcoidosis and active disease were treated with nebulized VIP for four weeks. VIP inhalation was safe, well-tolerated, and significantly reduced the production of TNF-α by cells isolated from bronchoalveolar lavage fluids. This was the first study to show the immunoregulatory effect of VIP in humans.

Rheumatoid Arthritis Research (Delgado et al., 2001) Published in Nature Medicine, this landmark study demonstrated that treatment with VIP significantly reduced incidence and severity of arthritis in an experimental model, completely abrogating joint swelling and destruction of cartilage and bone. The therapeutic effect was associated with downregulation of both inflammatory and autoimmune components of the disease.

Immunomodulatory Review (Delgado et al., 2004) A comprehensive review published in Pharmacological Reviews detailed VIP’s significance in immunomodulation, documenting its ability to suppress pro-inflammatory cytokines, generate regulatory T cells, regulate Th17 responses, and induce immune tolerance. The review established VIP as a viable candidate for therapeutic development across multiple inflammatory and autoimmune conditions.

Brain Structure and Mood Study (2021) A study in healthy females measured plasma VIP concentrations alongside MRI brain imaging and anxiety/depression symptoms. Results demonstrated associations between VIP levels and brain volume and functional connectivity in the amygdala, hippocampus, parahippocampus, and orbitofrontal cortex—regions linked to anxiety and depression. The findings support VIP’s role in mood regulation and brain health beyond disease states.

Limitations in Evidence

Most CIRS studies come from a single research group (Shoemaker). No large randomized placebo-controlled trials exist for VIP in CIRS. The CIRS diagnosis itself remains controversial in mainstream medicine. The FDA has questioned whether sufficient safety data exists for chronic VIP use. Other applications beyond CIRS remain largely investigational, though the biological plausibility and mechanistic consistency of VIP across systems is well established.

Dosing Protocol

VIP is typically administered as a nasal spray, allowing direct delivery to the brain through the olfactory pathway and rapid systemic absorption while bypassing first-pass liver metabolism. Dosing protocols are based primarily on clinical experience with CIRS patients.

Standard CIRS Protocol (Shoemaker) Phase Dose Frequency Duration Initial 50 mcg per spray 4 times daily 1 month Maintenance 100 mcg per spray 4 times daily Ongoing as needed

Spray into alternating nostrils throughout the day.

Prerequisites for CIRS Protocol

VIP should not be started until:

• Patient is in a mold-safe environment (ERMI less than 2 or HERTSMI-2 less than 11)
• Visual Contrast Sensitivity (VCS) test is passing
• MARCoNS (deep nasal staph) has been treated
• Other protocol steps have been completed (cholestyramine binding, inflammatory

markers addressed)

This sequencing is critical. Using VIP while still exposed to biotoxins or harboring nasal colonization can be counterproductive.

Alternative Protocols

• Lower starting doses (25 mcg per spray) for sensitive patients
• Twice-daily dosing for maintenance
• Courses of 1 to 6 months depending on response
• Some patients require ongoing maintenance therapy

Why Nasal Spray

• Bypasses first-pass liver metabolism
• Direct delivery to the brain via the olfactory pathway
• Rapid systemic absorption
• Mimics natural VIP production patterns
• This is the route used in all published CIRS protocols

Reconstitution for Research (Lyophilized Powder) VIP for CIRS treatment is typically obtained as a compounded nasal spray ready for use. If reconstituting lyophilized powder for research purposes: Step 1: Wipe the rubber stopper with an alcohol swab. Step 2: Draw the appropriate volume of sterile or bacteriostatic water into a syringe. Step 3: Direct the stream of water down the inside wall of the vial. Step 4: Allow the peptide to dissolve gently without aggressive agitation. Step 5: Once dissolved, transfer to a nasal spray bottle if using intranasally. Step 6: Label with date and concentration.

Research Draw Volumes – 5 mg Vial (5 mL reconstitution = 1 mg/mL)

Dose Volume 50 mcg 0.05 mL 100 mcg 0.10 mL 200 mcg 0.20 mL 500 mcg 0.50 mL Note: Nasal spray delivery is the standard route for VIP. Subcutaneous injection protocols are not well established for this compound.

Side Effects and Cautions

VIP is generally well tolerated. Dr. Shoemaker’s data on over 10,000 patients suggests VIP nasal spray produces few adverse effects.

Common Side Effects

• Nasal irritation or congestion
• Mild headache
• Nausea (uncommon)
• Flushing due to vasodilation (uncommon)

Serious Concerns (Rare)

• Diarrhea at high doses (VIP increases intestinal motility)
• Hypotension (low blood pressure) due to vasodilation
• Theoretical risk of pancreatitis (VIP affects pancreatic function)

FDA Concerns

The FDA has questioned whether sufficient safety data exists for chronic VIP use and has considered removing it from the list of compounds that can be compounded by pharmacies. This remains an evolving regulatory situation. As of this writing, compounding pharmacies can still prepare VIP nasal spray with a valid prescription.

Important Context

VIP is a regulatory peptide, not a stimulant or performance enhancer. Its role is to restore physiological balance. Because both excessive and deficient VIP signaling can be problematic, appropriate dosing, delivery method, and individual context matter. VIP should be used under medical supervision.

Contraindications and Precautions

Avoid

• Known hypersensitivity to VIP
• Pregnancy or breastfeeding (insufficient safety data)

• Active pancreatitis or history of severe pancreatic disease
• Active MARCoNS nasal colonization (treat first, per CIRS protocol)
• Still living or working in water-damaged buildings (address exposure first)

Do Not Combine With

• Blood pressure medications without monitoring (VIP causes vasodilation and may

compound hypotensive effects)

• Other strong vasodilators without medical supervision

Use with Caution

• Individuals with low blood pressure (VIP causes vasodilation)
• Those on antihypertensive medications (monitor for hypotension)
• People with inflammatory bowel disease (VIP affects gut motility)
• Anyone with a history of pancreatic issues

CIRS-Specific Contraindications

Using VIP prematurely in the CIRS protocol—before addressing biotoxin exposure, binding agents, and nasal colonization—may be ineffective or counterproductive. The Shoemaker protocol is sequential for documented reasons.

Comparison with Similar Compounds

Compound Primary Use Route Mechanism Best For VIP CIRS / Nasal spray VPAC1/2 CIRS, systemic inflammation / receptors, cAMP inflammation, vascular PAH KPV Gut / skin Subcutaneous / MSH pathway Localized inflammation oral gut/skin inflammation Thymosin α1 Immune Subcutaneous T-cell function Immune modulation deficiency, infections BPC-157 Gut / tissue Oral / Multiple Gut healing, healing subcutaneous pathways injury repair LL-37 Antimicrobial / Subcutaneous Membrane Infections, immune disruption biofilms

VIP is unique in its broad regulatory effects on inflammation, vascular function, and neuroendocrine systems simultaneously. For CIRS specifically, VIP is the established treatment based on published protocols. For general gut inflammation without CIRS, KPV or BPC-157 may be more accessible options. VIP requires a prescription in the United States and is best used under medical supervision within an established protocol.

VIP vs. KPV

Both VIP and KPV have anti-inflammatory properties, but they work through different pathways. VIP operates through VPAC1/2 receptors with broad systemic effects on vascular, immune, and neuroendocrine systems. KPV (Lys-Pro-Val) is a melanocyte-stimulating hormone fragment that primarily targets localized inflammation in the gut and skin. VIP is the established choice for CIRS and systemic inflammatory conditions; KPV is better suited for targeted gut and skin inflammation.

VIP vs. BPC-157

BPC-157 is a gastric peptide that promotes tissue healing through multiple pathways. VIP is a neuroendocrine regulator that restores systemic physiological balance. BPC-157 excels at healing specific injuries and gut damage; VIP addresses systemic inflammatory dysregulation. They are not interchangeable but may be complementary in some clinical situations.

Success Tips

Complete the Protocol First (CIRS Patients) If using VIP for CIRS, complete the earlier steps in the Shoemaker protocol. This includes removing yourself from mold exposure, using cholestyramine or Welchol to bind biotoxins, correcting MARCoNS, normalizing other inflammatory markers, and ensuring your environment tests safe. VIP is the finishing step, not the starting point.

Test Your Environment

Before starting VIP, confirm your home and workplace are safe using ERMI or HERTSMI-2 testing. Using VIP while being continuously re-exposed to biotoxins is ineffective.

Be Patient

VIP effects develop over weeks to months. Hormone normalization, inflammatory marker reduction, and symptom improvement are gradual. Do not expect immediate dramatic changes.

Monitor Key Markers

Track inflammatory markers (C4a, TGF-beta 1, MMP9) and hormones during VIP treatment to document response. This helps guide dosing and duration decisions.

Support Natural VIP Production

• Glycine supplementation may increase natural VIP production (bone broth is a dietary

source of glycine).

• Maintaining healthy circadian rhythms through consistent sleep–wake cycles supports

natural VIP regulation.

• Addressing chronic stress supports overall neuroendocrine function.

Foundation Matters

VIP is powerful but cannot overcome ongoing biotoxin exposure, poor sleep, chronic stress, or nutritional deficiencies. Address these fundamentals alongside peptide therapy.

Storage and Handling

Compounded Nasal Spray

• Refrigerate at 2–8°C (36–46°F).
• Use within the timeframe specified by the compounding pharmacy (typically 30–90

days).

• Do not freeze.
• Keep the spray tip clean between uses.

Lyophilized Powder

• Store in freezer at −20°C (−4°F) or colder for long-term storage.
• Protect from light and moisture.
• After reconstitution, refrigerate at 2–8°C and use within 28 days.
• Do not refreeze after reconstitution.
• If the solution becomes cloudy or contains particles, discard.

Travel

• Keep refrigerated when possible.
• A cooler with ice packs works for short trips.
• VIP is relatively stable but proper storage ensures potency throughout use.

Legal Status

United States

• VIP is available as a compounded medication with a prescription.
• The FDA has raised questions about compounded VIP and is reviewing its status.
• As of this writing, compounding pharmacies can still prepare VIP nasal spray with a

valid prescription.

• Not FDA-approved as a standalone drug for any specific indication.
• Aviptadil (synthetic VIP) received Emergency Use Authorization consideration during

COVID-19.

Research Status

• VIP has been used clinically in CIRS treatment since 2008.
• Published studies document efficacy and safety in this population.
• Multiple clinical studies in pulmonary hypertension, sarcoidosis, and inflammatory

conditions.

International

• Availability varies by country.
• Generally requires prescription or is available for research purposes.

The regulatory landscape for compounded VIP is evolving. Consult with a qualified healthcare provider familiar with VIP therapy for the most current information.

Frequently Asked Questions

What is CIRS and how do I know if I have it? Chronic Inflammatory Response Syndrome is a multi-system illness triggered by exposure to biotoxins, most commonly from water-damaged buildings. Symptoms include fatigue, cognitive dysfunction, pain, respiratory issues, and sensitivity to chemicals. Diagnosis involves specific lab markers (C4a, TGF-beta 1, MSH, VIP, MMP9, and others) combined with symptom patterns and exposure history. A qualified practitioner familiar with the Shoemaker protocol can evaluate you. Can I use VIP without completing the full CIRS protocol? This is not recommended. VIP works best after earlier protocol steps have addressed biotoxin exposure, binding, and nasal colonization. Using VIP prematurely may be ineffective and could mask ongoing problems. The protocol is sequential because systematic research showed this sequence produces the best outcomes. How long does VIP treatment take? Most patients use VIP for several months. Some require ongoing maintenance therapy. Duration depends on response, documented by symptom improvement and normalization of lab markers. Some patients can eventually discontinue VIP while maintaining improvements. Is VIP safe for long-term use? Dr. Shoemaker’s data on over 10,000 patients suggests VIP is well tolerated with few adverse effects. However, the FDA has questioned whether sufficient long-term safety data exists. This remains an area of ongoing regulatory discussion. Can VIP help conditions other than CIRS? Research suggests VIP has potential in various inflammatory and autoimmune conditions including rheumatoid arthritis, pulmonary hypertension, inflammatory bowel disease, sarcoidosis, and neuroinflammatory conditions. However, established protocols exist primarily for CIRS. Other applications remain investigational. Why is VIP given as a nasal spray instead of injection? Nasal administration provides direct delivery to the brain through the olfactory pathway, rapid systemic absorption, and avoids first-pass liver metabolism. This route has been used successfully in all published CIRS protocols and mimics natural VIP production patterns. Can VIP be combined with other peptides? VIP can be complementary to daytime nootropics like Semax, nighttime support like DSIP, and tissue-healing peptides like BPC-157. These compounds work through different mechanisms. However, all combinations are experimental and should be discussed with a qualified healthcare provider. Does VIP require a prescription? In the United States, VIP nasal spray requires a prescription and is prepared by compounding pharmacies. Lyophilized VIP is also available as a research peptide. For CIRS treatment, medical supervision is strongly recommended. Can VIP help with anxiety or mood issues? Research has demonstrated associations between VIP levels and brain structure and function in regions linked to anxiety and depression. VIP also regulates circadian rhythms, which influence mood stability. In CIRS patients, VIP treatment has been associated with cognitive improvement and symptom reduction. However, VIP is not currently established as a standalone treatment for mood disorders.

References

1. Shoemaker RC, House D, Ryan JC. Vasoactive intestinal polypeptide (VIP) corrects chronic inflammatory response syndrome (CIRS) acquired following exposure to water-damaged buildings. Health. 2013;5(3):396–401. 2. Ryan J, Shoemaker R. RNA-Seq on patients with chronic inflammatory response syndrome (CIRS) treated with vasoactive intestinal polypeptide (VIP) shows a shift in metabolic state and

innate immune functions that coincide with healing. Medical Research Archives. 2016;4(7):1– 11. 3. Shoemaker R, Katz D, McMahon S, Ryan J. Intranasal VIP safely restores volume to multiple grey matter nuclei in patients with CIRS. Internal Medicine Review. 2017;3(4):1–14. 4. Petkov V, Mosgoeller W, Ziesche R, et al. Vasoactive intestinal peptide as a new drug for treatment of primary pulmonary hypertension. Journal of Clinical Investigation. 2003;111(9):1339–1346. 5. Delgado M, Abad C, Martinez C, Leceta J, Gomariz RP. Vasoactive intestinal peptide prevents experimental arthritis by downregulating both autoimmune and inflammatory components of the disease. Nature Medicine. 2001;7:563–568. 6. Delgado M, Pozo D, Ganea D. The significance of vasoactive intestinal peptide in immunomodulation. Pharmacological Reviews. 2004;56(2):249–290. 7. Gonzalez-Rey E, Delgado M. Role of vasoactive intestinal peptide in inflammation and autoimmunity. Current Opinion in Investigational Drugs. 2005;6:1116–1123. 8. Prasse A, Zissel G, Lützen N, et al. Inhaled vasoactive intestinal peptide exerts immunoregulatory effects in sarcoidosis. American Journal of Respiratory and Critical Care Medicine. 2010;182(4):540–548. 9. Leceta J, Gomariz RP, Martinez C, et al. Vasoactive intestinal peptide regulates Th17 function in autoimmune inflammation. Neuroimmunomodulation. 2007;14:134–138. 10. Delgado M, Chorny A, Gonzalez-Rey E, Ganea D. Vasoactive intestinal peptide generates CD4+CD25+ regulatory T cells in vivo. Journal of Leukocyte Biology. 2005;78:1327–1338. 11. Martínez C, Juarranz Y, Gutiérrez-Cañas I, et al. A clinical approach for the use of VIP axis in inflammatory and autoimmune diseases. International Journal of Molecular Sciences. 2019;21(1):65. 12. Said SI, Rosenberg RN. Vasoactive intestinal polypeptide: abundant immunoreactivity in neural cell lines and normal nervous tissue. Science. 1976;192:907–908. 13. Henning RJ, Sawmiller DR. Vasoactive intestinal peptide: cardiovascular effects. Cardiovascular Research. 2001;49(1):27–37. 14. Nussdorfer GG, Malendowicz LK. Role of VIP, PACAP, and related peptides in the regulation of the hypothalamo-pituitary-adrenal axis. Peptides. 1998;19(8):1443–1467. 15. Brenneman DE, Glazner GW, Hill JM, et al. VIP and activity-dependent neuroprotection. Annals of the New York Academy of Sciences. 1998. 16. Cai J, Chen Q, Mehrabi Nasab E, Athari SS. Immunomodulatory effect of N-acetyl-seryl- aspartyl-proline and vasoactive intestinal peptide on chronic obstructive pulmonary disease pathophysiology. Fundamental and Clinical Pharmacology. 2022;36(6):1005–1010.