The Role of the Hypothalamic-Pituitary-Adrenal Axis in Susceptibility to Autoimmune/Inflammatory Disease

Abstract

The central nervous system (CNS) affects the immune system through endocrine, paracrine, and neuronal mechanisms. The immune system in turn communicates with the CNS through many of the same mechanisms. Evidence that this bidirectional communication plays a vital role in susceptibility to inflammatory and infectious disease is derived largely from animal models in which the communication has been interrupted or reconstituted surgically, pharmacologlcally, or on a preexisting genetic basis. The advantage of animal models for studying the pathophysiologic relevance of such connections is that the systems can be manipulated at several levels and at different times in relation to development of the inflammatory disease and the outcome of the manipulation can be quantified. While in vitro studies may be used to further define the subcellular and molecular mechanisms of these interactions, only an intact organism, in which the central nervous system is connected to the immune system, can be used to fully define the nature of these interconnections. This review describes approaches to studying CNS-immune system interactions, using relatively inflammatory-susceptible and inflammatory-resistant Lewis and Fischer rats as models for evaluating the role of the HPA axis in susceptibility to inflammatory disease.