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Potent Anti-Inflammatory and Immunomodulatory Activity: Research suggests that Vasoactive Intestinal Peptide exhibits potent anti-inflammatory and immunomodulatory effects, making it a promising candidate for treating inflammatory and autoimmune diseases [1].

Studies show that VIP regulates innate immunity by inhibiting inflammatory cytokines and chemokines from macrophages, microglia, and dendritic cells, while reducing co-stimulatory molecule expression on antigen-presenting cells. In adaptive immunity, VIP shifts the Th1/Th2 balance by promoting anti-inflammatory Th2 responses and enhancing regulatory T cell (Treg) activity [2].

Studies in rheumatoid arthritis models demonstrate VIP’s ability to reduce systemic pathogenic antibodies and inflammation. Advances in VIP analogs and delivery methods highlight its potential for precision medicine in managing immune-related disorders [3].

Lung Protective Effects: VIP research demonstrates significant lung protective effects, including bronchodilation, surfactant support, and alveolar cell protection. VIP acts as a neuromodulator in the airway, relaxing smooth muscles and reducing inflammation, making it a potential treatment for asthma and COPD. Advances in VIP analogs, such as IK312532, and inhaler systems have improved its clinical viability [4].

In COVID-19 respiratory failure, the synthetic VIP Aviptadil showed promising results, doubling survival odds at 60 days and reducing cytokine release and respiratory distress. These findings highlight VIP’s potential in protecting lung function and treating severe pulmonary conditions with an acceptable safety profile [5].

Gastrointestinal Regulation: Research indicates that VIP Peptide plays a crucial role in gastrointestinal regulation and exhibits potent anti-colitic effects. Studies have shown that the peptide regulates gut motility, ion secretion, nutrient absorption, and immune responses, thereby contributing to overall gastrointestinal homeostasis.

In a TNBS-induced colitis model, VIP significantly reduced inflammation, weight loss, and intestinal damage by downregulating pro-inflammatory cytokines like TNF-α, IL-1, and IL-6, as well as Th1-driven autoimmune responses. It also decreased disease recurrence when administered after disease onset [6]. These findings highlight VIP’s potential as a therapeutic candidate for inflammatory bowel diseases like Crohn’s disease, offering both prophylactic and therapeutic benefits in managing gut inflammation [7].

Metabolic effects: Research shows that VIP has important effects on metabolism, especially in regulating glucose and cellular energy. Studies have shown that it helps stimulate insulin secretion in response to glucose through VPAC2 receptors and supports the growth of islet β-cells, making it a promising option for treating type 2 diabetes [8].

VIP also improves fatty acid uptake, lipid metabolism, and glucose use in cytotrophoblast cells, which benefits placental function and fetal development. While these findings suggest VIP could be useful for treating metabolic disorders and pregnancy-related complications, its short half-life limits its clinical use [9].

Cardiovascular Actions: Studies suggest that VIP plays a critical role in cardiovascular regulation, acting as a potent vasodilator that is 50–100 times stronger than acetylcholine. VIP enhances coronary blood flow, reduces vascular resistance, and improves cardiac contractility and heart rate. It also supports ventricular-vascular coupling by lowering arterial pressure [10].

During atrial fibrillation, elevated serum VIP levels correlate with low-voltage areas in the left atrium, suggesting its potential as a noninvasive biomarker for improved clinical management. These findings highlight VIP’s importance in maintaining cardiovascular function and its diagnostic potential [11].

Potential Tissue Protective and Anti-Cell Death Actions: Research on Vasoactive Intestinal Peptide has demonstrated its tissue-protective and anti-cell-death properties through its immunoregulatory and anti-inflammatory effects. Studies in rheumatoid arthritis models have shown that VIP reduces pathogenic antibody production and promotes regulatory T cell activity, mitigating tissue damage [3].

In lambs, VIP administration decreased pro-inflammatory cytokines and lipopolysaccharide (LPS) levels, reducing systemic inflammation. While VIP did not affect tight junction mRNA expression, its ability to lower inflammation highlights its potential in protecting tissues from damage in inflammatory conditions [12].