CNS/IMMUNE SYSTEM INTERACTION--GENETICS/RELEVANCE TO BEHAVIORAL ILLNESS

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The research of the Section on Neuroendocrine Immunology and Behavior focuses on several aspects of central nervous system - immune system interactions in animals and humans. These studies aim at defining the pathophysiological relevance and underlying mechanisms of neuroimmune interactions, with particular focus on hypothalamic-pituitary-adrenal (HPA) axis - immune system interactions. Project 1., "Genetic linkage and segregation studies in inbred rat strains", focuses on identifying the genetic basis for co-inherited traits of inflammatory disease susceptibility, HPA axis dysregulation and patterns of behavioral responses to stress in inbred rat strains, using genetic linkage and segregation. Current findings suggest several linkages with both the behavioral and inflammation phenotypes we are examining. In these studies additional animals must be genotyped in order to confirm the significance of these possible linkage sites. Project 2., "Whole-blood cytokine production and glucocorticoid sensitivity in humans" focuses on defining in human subjects the relationship of variations in HPA axis responsiveness to variations in immune system responsiveness and symptoms of affective disorder. This study utilizes a whole blood cytokine production and glucocorticoid sensitivity assay which we have found to be sensitive to physiological variations in ambient glucocorticoid levels. Most recently we have found differences in glucocorticoid sensitivity in different clinical sub-populations of multiple sclerosis patients. Project 3., "Hypothalamic intracerebroventricular transplantation of neuronal tissue: effects on experimental models of autoimmune/inflammatory disease". This project focuses on defining the pathophysiologic consequences of reconstitution of the HPA axis by intracerebroventricular transplantation of fetal neuronal tissue in autoimmune/inflammatory diseases in inbred rat strains. Results indicate that fetal neuronal tissue transplantation differentially affects expression of different models of experimentally-induced inflammatory/autoimmune diseases, with the major specific effect on suppression of innate (non-thymic dependent) models of inflammation. This suppression in part appears to act through the HPA axis.