Circadian rhythms on hypothalamic-pituitary-adrenal axis hormones and cytokines of collagen induced arthritis in rats

This study is designed to identify whether circadian rhythms of the hormones of the hypothalamic-pituitary-adrenal (HPA) axis are associated with corresponding circadian fluctuations in cytokines in a rat model of collagen-induced arthritis (CIA). CIA is induced in Wistar rats by an intradermal injection of bovine type II collagen emulsified with complete adjuvant at the left foot. On day 33, in both the CIA and the control rats, circulating adrenocorticotropin hormone (ACTH) and corticosterone, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and IL-lbeta were evaluated at 6 h intervals from 00:00 to 24:00, and analyzed by statistics and cosinor-rhythmometry. The results showed that plasma corticosterone in CIA rats had a trough at 18:00 and reached a peak at 06:00 significantly. While peak values were presented in TNF-alpha at 24:00 and in IL-6 from 06:00 and 18:00 to 24:00. CIA rats exhibit abnormal circadian rhythms, with degrading amplitudes of corticosterone and IL-6, elevating amplitude of TNF-alpha, and marked phase shifts in corticosterone and IL-6. Our investigation suggests that the disorders of HPA axis in CIA rats may be related to the influence of inflammation mediators on hypothalamic centers. The circadian rhythms of hormones and cytokines in CIA rats may be reset due to the defective function of the HPA axis. (C) 2004 Elsevier Ltd. All rights reserved.