Drug – bio-affecting and body treating compositions – In vivo diagnosis or in vivo testing – Magnetic imaging agent
Patent
1988-11-30
1991-04-09
Nutter, Nathan M.
Drug, bio-affecting and body treating compositions
In vivo diagnosis or in vivo testing
Magnetic imaging agent
514 2, 514 21, 514825, A61K 4900, G01N 3100, G01N 3348
Patent
active
050063308
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: 4801612 (1989-01-01), Wei et al.
Hom et al, Chemical Abstracts, 109:108768q, p. 475 (1988).
Kennett et al, Chemical Abstracts, 106:188913j, p. 63 (1987).
Wick et al, Immunology Today, vol. 6, No. 12, pp. 359-364 (1985).
Wick et al, Immunology Letters, 16, pp. 249-258 (1987).
Kroemer et al, Immunology Today, vol. 9, No. 6, pp. 163-165 (1988).
Wick et al, Genetically Determined Thyroid Alterations, pp. 113-136.
Schauenstein et al, The Journal of Immunology, vol. 139, No. 6, pp. 1830-1833 (1987).
Fassler et al, The Journal of Immunology, vol. 136, No. 10, pp. 3657-3661 (1986).
Jacobs et al, The Journal of Immunology, vol. 141, No. 9, pp. 2967-2974 (1988).
Cole et al, Science, vol. 160, pp. 1357-1358.
Waterston, Science, vol. 170, pp. 1108-1110 (1970).
Sorkin et al, Proceedings of the Society for Experimental Biology and Medicine 150, pp. 466-470 (1975).
Chrousos George P.
Gold Philip W.
Sternberg Esther M.
Wilder Ronald L.
Nutter Nathan M.
The United States of America as represented by the of the Depart
LandOfFree
Evaluative means for detecting inflammatory reactivity does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Evaluative means for detecting inflammatory reactivity, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Evaluative means for detecting inflammatory reactivity will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2033247