INTRACEREBROVENTRICULAR TRANSPLANTATION OF EMBRYONIC NEURONAL TISSUE FROM INFLAMMATORY RESISTANT INTO INFLAMMATORY SUSCEPTIBLE RATS SUPPRESSES SPECIFIC COMPONENTS OF INFLAMMATION

To more directly define the role of central nervous system factors in susceptibility to peripheral inflammatory disease, we examined the eff ect of intracerebroventricular transplantation of neuronal tissue from inflammatory resistant into inflammatory susceptible rats on subcutan eous carrageenan-induced inflammation (a measure of innate immunity), and on the relative percentage of naive and memory T helper cells in p eripheral blood (a measure of the anamnestic immune response). Female inflammatory disease susceptible Lewis (LEW/N) rats transplanted with hypothalamic tissue from inflammatory resistant Fischer (F344/N) rats exhibited > 85% decrease in carrageenan inflammation compared to naive LEW/N rats, LEW/N rats transplanted with F344/N spinal cord, or sham- operated animals. LEW/N rats transplanted with LEW/N hypothalamic tiss ue exhibited > 50% decrease in carrageenan inflammation. In contrast, intracerebroventricular transplantation of neuronal tissue did not aff ect the characteristically twofold higher percentage of naive versus m emory T helper cells in LEW/N rats, suggesting that the central nervou s system (CNS) and hypothalamus play a greater role in the innate infl ammatory response than in the acquired immune processes. Grafted tissu e survived well and did not show extensive gliosis or inflammation. Co mpared to naive LEW/N rats, LEW/N rats transplanted with F344/N or LEW /N hypothalamic tissue expressed significantly greater hypothalamic co rticotropin releasing hormone mRNA. LEW/N rats transplanted with F344/ N hypothalamic tissue also showed significant increases in plasma cort icosterone responses to lipopolysaccharide. These data indicate that i ntracerebroventricular transplantation of fetal hypothalamic tissue fr om inflammatory resistant into inflammatory susceptible rats suppresse s peripheral inflammation partially through hypothalamic factors. Thes e findings have implications for understanding the contribution of spe cific neuronal tissue in regulation of components of the immune/inflam matory response and in susceptibility to inflammatory disease. Further more, this model could be used in the development of potential new tre atments for inflammatory/autoimmune diseases aimed specifically at sit es within the CNS. (C) 1997 Academic Press.