Drug – bio-affecting and body treating compositions – In vivo diagnosis or in vivo testing – Magnetic imaging agent
Patent
1989-09-25
1993-05-11
Nutter, Nathan M.
Drug, bio-affecting and body treating compositions
In vivo diagnosis or in vivo testing
Magnetic imaging agent
424 851, 424 852, 424 854, 424 855, 424 856, 424 857, 514805, 514825, 5148851, 514886, 514884, 435975, 436 2, 206569, G01N 100, G01N 3348, A61K 3760, A61K 4505
Patent
active
052099202
ABSTRACT:
Inbred Lewis (LEW/N) female rats develop an arthritis in response to Group A streptococcal cell wall peptidoglycanpolysaccharide (SCW) which mimics human rheumatoid arthritis. Histocompatible Fischer (F344/N) rats, on the other hand, do not develop arthritis in response to the same SCW stimulus. To evaluate this difference in inflammatory reactivity between the two strains, the function of the hypothalamic-pituitary-adrenal axis and its ability to modulate the development of the inflammatory response was studied. It has been found that, in contrast to F344/N rats, LEW/N rats had markedly impaired plasma ACTH and corticosterone responses to SCW, recombinant human Interleukin-1 alpha (IL-1 alpha), the serotonin agonist, quipazine, and synthetic rat corticotropin-releasing hormone (CRH). In addition, LEW/N rats compared to F344/N rats had smaller adrenal glands and larger thymuses. Treatment of LEW/N rats with replacement doses of dexamethasone decreased the severity of their SCW-induced arthritis. Conversely, treatment of F344/N rats with the glucocorticoid receptor antagonist, RU 486, or the serotonin (5-HT.sub.2) antagonist, LY53857, was associated with development of severe inflammatory disease, including arthritis, in response to SCW. These findings support the concept that susceptibility of LEW/N rats to SCW arthritis is related to abnormal hypothalamic-pituitary-adrenal (HPA) axis responsiveness to inflammatory and other stress mediators and that resistance of F344/N rats to SCW arthritis is regulated by an intact HPA axis-immune system feedback loop.
REFERENCES:
patent: 5006330 (1991-04-01), Sternberg et al.
Gross et al. "A Radio immunoassay for Plasma Corticosterone" Steroids, 20, 1972, pp. 681-695.
Chrousos George P.
Gold Philip W.
Sternberg Esther M.
Wilder Ronald L.
Nutter Nathan M.
The United States of America as represented by the United States
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