THE SIGNIFICANCE OF VASOACTIVE INTESTINAL POLYPEPTIDE (VIP) IN IMMUNOMODULATION

Evidence for VIP influences on immune function comes from studies demo nstrating VIP-ir nerves in lymphoid organs in intimate anatomical asso ciation with elements of the immune system, the presence of high-affin ity receptors for VIP, and functional studies where VIP influences a v ariety of immune responses. Anatomical studies that examine the relati onship between VIP-containing nerves and subpopulations of immune effe ctor cells provide evidence for potential target cells. Additionally, the presence of VIP in cells of the immune system that also possess VI P receptors implies an autocrine function for VIP. The functional sign ificance of VIP effects on the immune system lies in its ability to he lp coordinate a complex array of cellular and subcellular events, incl uding events that occur in lymphoid compartments, and in musculature a nd intramural blood circulation. Clearly, from the work described in t his chapter, the modulatory role of VIP in immune regulation is not we ll understood. The pathways through which VIP can exert an immunoregul atory role are complex and highly sensitive to physiological condition s, emphasizing the importance of in vivo studies. Intracellular events following activation of VIP receptors also are not well elucidated. T here is additional evidence to suggest that some of the effects of VIP on cells of the immune system are not mediated through binding of VIP to its receptor. Despite our lack of knowledge regarding VIP immune r egulation, the evidence is overwhelming that VIP can interact directly with lymphocytes and accessory cells, resulting in most cases, but no t always in cAMP generation within these cells, and a subsequent casca de of intracellular events that alter effector cell function. VIP appe ars to modulate maturation of specific populations of effector cells, T cell recognition, antibody production, and homing capabilities. Thes e effects of VIP are tissue-specific and are probably dependent on the resident cell populations within the lymphoid tissue and the surround ing microenvironment. Different microenvironments within the same lymp hoid tissue may influence the modulatory role of VIP also. Effects of VIP on immune function may result from indirect effects on secretory c ells, endothelial cells, and smooth muscle cells in blood vessels, duc ts, and respiratory airways, Influences of VIP on immune function also may vary depending on the presence of other signal molecules, such th at VIP alone will have no effect on a target cell by itself, but may g reatly potentiate or inhibit the effects of other hormones, transmitte rs, or cytokines. The activational state of target cells may influence VIP receptor expression in these cells, and therefore, may determine whether VIP can influence target cell activity. Several reports descri bed in this chapter also indicate that VIP contained in neural compart ments is involved in the pathophysiology of several disease states in the gut and lung. Release of inflammatory mediators by cells of the im mune system may destroy VIP-containing nerves in inflammatory bowel di sease and in asthma. Loss of VIPergic nerves in these disease states a ppears to further exacerbate the inflammatory response. These studies indicate that altered VIP concentration can have significant consequen ces in terms of health and disease. In addition, the protective effect s of VIP from tissue damage associated with inflammatory processes des cribed in the lung also may be applicable to other pathological condit ions such as rheumatoid arthritis, anaphylaxis, and the swelling and e dema seen in the brain following head trauma. While VIP degrades rapid ly, synthetic VIP-like drugs may be developed that interact with VIP r eceptors and have similar protective effects. Synthetic VIP-like agent s also may be useful in treating neuroendocrine disorders associated w ith dysregulation of the hypothalamic-pituitary-adrenal axis, and pitu itary release of prolactin. Copyright (C) 1996.