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Updated: Jul 29, 2026

The Use of Mouse Splenocytes to Assess Pathogen-associated Molecular Pattern Influence on Clock Gene Expression
Published on: July 24, 2018
Circadian rhythms and arthritis
Maurizio Cutolo1, Alfonse T Masi
1Research Laboratory, Division of Rheumatology, Department of Internal Medicine, Università degli Studi di Genova, Viale Benedetto XV 6, 16132 Genova, Italy. mcutolo@unige.it
Abstract:
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.
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