Circadian rhythms and arthritis.

The clinical symptoms of rheumatoid arthritis (RA) show a circadian variation; joint stiffness and pain are more prominent in the early morning. An altered functioning of the hypothalamic-pituitary-adrenal axis (cortisol) and of the pineal gland (melatonin) seems to be important factors in the perpetuation and clinical circadian symptoms of RA. Consistently, human proinflammatory cytokine production exhibits a diurnal rhythmicity with peak levels during the night and early morning, at a time when plasma cortisol (anti-inflammatory) is lowest and melatonin (proinflammatory) is highest. Sex hormones also seem to be involved in circadian rhythms of RA symptoms. Increased pain intensity and sleep disturbances are observed during the luteal phase in patients who have RA, when estrogen (and progesterone) levels would be higher than in the follicular phase. The occurrence of circadian rhythms of the inflammatory reaction suggest important implications for scheduling activities of daily living, for measurements in clinical trials, and possibly for the time at which antirheumatic drugs--including corticosteroids and nonsteroidal anti-inflammatory drugs--are administered.