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 effect of intracerebroventricular transplantation of neuronal tissue from inflammatory resistant into inflammatory susceptible rats on subcutaneous carrageenan-induced inflammation (a measure of innate immunity), and on the relative percentage of naive and memory T helper cells in peripheral 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 tissue exhibited > 50% decrease in carrageenan inflammation. In contrast, intracerebroventricular transplantation of neuronal tissue did not affect the characteristically twofold higher percentage of naive versus memory T helper cells in LEW/N rats, suggesting that the central nervous system (CNS) and hypothalamus play a greater role in the innate inflammatory response than in the acquired immune processes. Grafted tissue survived well and did not show extensive gliosis or inflammation. Compared to naive LEW/N rats, LEW/N rats transplanted with F344/N or LEW/N hypothalamic tissue expressed significantly greater hypothalamic corticotropin releasing hormone mRNA. LEW/N rats transplanted with F344/N hypothalamic tissue also showed significant increases in plasma corticosterone responses to lipopolysaccharide. These data indicate that intracerebroventricular transplantation of fetal hypothalamic tissue from inflammatory resistant into inflammatory susceptible rats suppresses peripheral inflammation partially through hypothalamic factors. These findings have implications for understanding the contribution of specific neuronal tissue in regulation of components of the immune/inflammatory response and in susceptibility to inflammatory disease. Furthermore, this model could be used in the development of potential new treatments for inflammatory/autoimmune diseases aimed specifically at sites within the CNS.
Misiewicz
B
B
Clinical Neuroendocrinology Branch, National Institute of Mental Health, Bethesda, Maryland 20892, USA.
Poltorak
M
M
Raybourne
R B
RB
Gomez
M
M
Listwak
S
S
Sternberg
E M
EM
D000818:Animals; D002351:Carrageenan; D002552:Cerebral Ventricles / Q000502:physiology*; D005260:Female; D016332:Fetal Tissue Transplantation; D020022:Genetic Predisposition to Disease; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007249:Inflammation / Q000139:chemically induced / Q000235:genetics* / Q000517:prevention & control*; D008070:Lipopolysaccharides / Q000494:pharmacology; D018655:Lymphocyte Count; D009417:Nerve Tissue / Q000196:embryology*; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000473:pathology
D008070:Lipopolysaccharides; D002351:Carrageenan