Neuroendocrine and other factors in the regulation of inflammation. Animal models

Abstract

A variety of animal models have been used to study the role of neuroendocrine responses in various aspects of autoimmune/inflammatory disease. Complex models of autoimmune disease, such as inflammatory arthritis in rats and thyroiditis in chickens, indicate a role for blunted HPA axis and dysregulated sympathoneuronal responses in susceptibility to autoimmune disease. A variety of approaches including pharmacological, surgical (ablation, transplantation), genetic linkage and segregation studies have been used to identify factors contributing to the phenotypes of susceptibility or resistance to inflammatory/autoimmune disease. Innate inflammation, or the earliest nonspecific form of the inflammatory response, which is characterized by fluid exudation and migration of immune cells to inflammatory sites, is a subtrait of these forms of inflammatory disease. Genetic linkage and segregation studies in inflammatory susceptible and resistant rat strains indicate that this subtrait is multigenic and polygenic; that is, that multiple loci on multiple chromosomes, each with a weak effect, control this trait, and that there is a large environmental component to the variability of this trait. Such information derived from animal studies can be used to target candidate genes for further study and to inform the design of human studies.