Circadian Rhythms and the Treatment of Rheumatoid Arthritis

Circadian clocks are ubiquitous biological timing systems that drive roughly 24 rhythms of our behavior (e.g., sleep/wake, feeding/fasting cycles) and physiology (e.g., metabolism, hormonal system, immune functions) through daily adjustments to environmental day and night cycles. Besides the rhythmic regulation of physiological processes, the circadian clockwork has been increasingly recognized to determine the daily variation in pathological symptoms and severity, particularly in autoimmune diseases including Rheumatoid Arthritis (RA). RA is a chronic inflammatory disease caused by the body’s immune system attacking its own tissues and joints, resulting in major symptoms such as joint pain and stiffness. In most RA patients, the autoimmune symptoms are pronounced in the morning and are mediated by circadian rhythms of leukocyte recruitment to inflamed tissues, release of pro-inflammatory cytokines (e.g., IL-6, TNF-α), and immune-modulatory hormone levels (e.g., glucocorticoid, melatonin). With the growing knowledge of the circadian etiology of RA clinical symptoms, here, we will briefly discuss recently established chronotherapeutic concepts as well as approaches to improve outcomes of RA treatment.

Keywords: Circadian clock; Rheumatoid arthritis; Autoimmune diseases; Glucocorticoid, Melatonin; Chronotherapeutic treatment