Vasoactive intestinal peptide inhaled agonists: potential role in respiratory therapeutics

Purpose of review: Vasoactive Intestinal Peptide (VIP) is a neuropeptide, expressed by lymphoid as well as neural cells, which has diverse effects on the cellular mediators of inflammation and immunity and is also a potent neurotransmitter. VIP seems to have a major role in the homeostasis of the respiratory system, while several studies, including clinical trials, suggest that VIP-inhaled agonists could be used in respiratory therapeutics. In this review, we provide an introduction to the field of VIP research geared to clinical and research pulmonologists. Recent Findings: As a neurotransmitter, VIP exerts a potent bronchodilatory and vasodilatory effect and also is supposed to induce the house-keeping mucus secretion by submucosal glands. On the other hand, it has immunomodulatory functions which include humoral immune response suppression, inhibition of vascular and bronchial remodeling and inflammation and attenuation of the cigarette smoke extract-induced apoptotic death of alveolar L2 cells. Recent research on a wide spectrum of lung diseases including asthma, chronic obstructive pulmonary disease, cystic fibrosis, pulmonary hypertension, and sarcoidosis indicates a potential therapeutic role of a VIP agonist. Simultaneously, novel stabilized inhaled VIP agonists and drug delivery systems have been proposed as a promising candidate alternative drug with minimized side effects. These data are supported by the results of certain, limited clinical trials which have already been conducted. Conclusion: Ongoing research continues to clarify the immunomodulatory effects of VIP and to confirm animal findings with human studies. A major challenge for investigators will be to determine whether stabilized inhaled-VIP agonists could be used in respiratory therapeutics.