European Journal of Psychotraumatology (Sep 2012)
Circadian profiles of cytokines and HPA axis activity in patients with rheumatoid arthritis: endocrine changes and clinical improvement following treatment with timed-release tablet of prednisone
Abstract
Background : Joint stiffness in rheumatoid arthritis (RA) is worse in the morning and has been associated with increased secretion of the pro-inflammatory cytokine IL-6 and with decreased secretion of cortisol, suggesting that clinical symptoms may be related to hormonal and immune circadian variations. We measured 24-h blood profiles of IL-6 and cortisol in patients with RA to determine any changes in IL-6 and cortisol following a 2-week course of prednisone administered orally in a specially designed timed-release tablet (TRT). Methods : Nine patients with active RA were clinically assessed and had 24-h blood sampling before and after a 2-week course of TRT prednisone (5 mg per day). Patients took the TRT orally at 2200 h, and the prednisone was released at 0200 h. Changes in circadian variation in cortisol and IL-6 and clinical measures were compared using random coefficient regression modelling and Wilcoxon matched-pairs signed-rank test. Results : IL-1ra, IL-1β, IL-4 and TNF showed no circadian variation prior to TRT prednisone. Significant alterations in circadian profiles and concentrations of IL-6 and cortisol were observed following TRT prednisone. The peak value of IL-6 fell from 42.5 to 21.3 pg/ml and occurred earlier (0134 h compared to 0827 h) (p < 0.005). Following TRT prednisone, the peak value of cortisol increased from 14.1 to 19.3 µg/dl, and the trough fell from 2.9 to 2.1 µg/dl (p < 0.001). There was a close correlation between reduction of IL-6 and improvement in morning joint stiffness following TRT. Conclusions : These experiments cast new light on circadian patterns of cytokines and hormones in a chronic inflammatory disease. We propose that these changes in IL-6 and cortisol, prior to the onset of morning joint stiffness, are functionally important in mediating the improvement in joint stiffness following prednisone in patients with RA.
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