Prevention of immune-mediated arthritis in cholestatic rats: involvement of endogenous glucocorticoids

Gastroenterology. 1994 Nov;107(5):1469-74. doi: 10.1016/0016-5085(94)90551-7.

Abstract

Background/aims: Hyporesponsiveness of the hypothalamic-pituitary-adrenal axis to stress is implicated in the development of immune-mediated arthritis in rats. This study investigated whether the documented hyporesponsiveness of the hypothalamic-pituitary-adrenal axis in cholestatic rats predisposes them to immune-mediated arthritis.

Methods: Bile duct-resected (BDR) and sham-resected rats were injected with either complete Freund's adjuvant (CFA; to induce immune-mediated arthritis) or incomplete Freund's adjuvant (IFA) at the time of laparotomy. Arthritis development was then assessed using a clinical arthritis score, and plasma corticosterone levels were determined.

Results: CFA-injected sham-resected rats developed arthritis, whereas CFA-injected BDR rats did not. CFA- and IFA-injected BDR rats had 14- and 6-fold higher levels of plasma free corticosterone than respective sham-resected controls. In addition, CFA-injected BDR rats treated with the glucocorticoid receptor antagonist RU 486 developed severe arthritis.

Conclusions: Cholestasis because of BDR prevents the occurrence of immune-mediated arthritis and is associated with elevated plasma free corticosterone levels. Furthermore, CFA-injected BDR rats treated with RU 486 developed severe arthritis. Therefore, high-circulating glucocorticoid levels seem to result in a relative state of immunosuppression in BDR rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Arthritis, Experimental / immunology
  • Arthritis, Experimental / prevention & control*
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / prevention & control
  • Bile Ducts / surgery
  • Cholestasis / metabolism*
  • Cholestasis / physiopathology
  • Corticosterone / blood
  • Freund's Adjuvant
  • Glucocorticoids / physiology*
  • Hypothalamo-Hypophyseal System / physiopathology
  • Male
  • Mifepristone / pharmacology
  • Pituitary-Adrenal System / physiopathology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Glucocorticoid / antagonists & inhibitors
  • T-Lymphocytes / immunology

Substances

  • Glucocorticoids
  • Receptors, Glucocorticoid
  • Mifepristone
  • Freund's Adjuvant
  • Corticosterone