ABSTRACT
Departments of Medicine and Microbiology-Immunology, University of California Medical Center, San Francisco, CA 94143-0711, USA
Vasoactive intestinal peptide (VIP) and the related pituitary adenylyl cyclase-activating peptide (PACAP) are derived from and act on many different types of cells (Dorsam et al., 2000). Our present understanding of the breadth of physiological and pathological contributions of these mediators has superceded the circumstantial identification of their original sources and biological effect, which led to assignment of the name of each peptide. VIP is generated, stored and released by numerous cellular constituents of the nervous system and by many different types of leukocytes, including T cells, mast cells, basophils, macrophages and eosinophils (Aliakbari et al., 1987; Hernanz et al., 1989; Goetzl et al., 1998; Schmidt-Choudhury et al., 1999). Neural, endocrine and, most recently, immune effects of VIP have been recognized in vitro and in vivo in many mammalian species (Figure 5.1). The diverse activities of VIP released from cholinergic, adrenergic and other nerves are observed both during development and as trophic influences in adults. Endocrine activities of VIP are vital in hypothalamic-pituitary and pancreatic functions, and may extend to reproductive functions as well (Goetzl and Sreedharan, 1992). In immunity, the results of in vitro studies initially directed attention to subsets of B cells and T cells, which express G-protein-coupled receptors for VIP. The first detectable consequences of VIP actions were on T cells and encompassed enhanced adhesion and migration, decreased activation-induced apoptosis, distinctively altered generation of diverse cytokines and modified regulation of T cell-dependent B cell production of several immunoglobulins (Goetzl et al., 1995). The Th2 subset of murine CD4+ T cells is an important principal source and target of VIP. More recently, data to be presented here show that one VIP receptor transduces a dominant immune signal capable of controlling the Th1/Th2 balance and consequently the immune phenotype of mice.
