The Potential of Circadian Realignment in Rheumatoid Arthritis

In this short review, we discuss evidence supporting the modulation of peripheral circadian systems as a therapeutic strategy for rheumatoid arthritis (RA). We first review the role of proinflammatory cytokines and oxidative stress, two of the primary mediators of chronic inflammation in RA, and their regulation by circadian clock machinery. We further highlight the role of environmental and metabolic signals in regulating the central and peripheral circadian clocks, with an emphasis on seasonal variations in photoperiod and rhythmic metabolic input, respectively. Finally, we hypothesize that the entrainment and realignment of peripheral clock rhythms have the ability to modulate these mediators, improving clinical outcomes in RA patients. Our discussion emphasizes the use of light therapy and time-restricted feeding for entraining peripheral clocks either via the entrainment of the central circadian clock in suprachiasmatic nuclei (SCN) or directly by uncoupling the peripheral circadian clocks from SCN. In doing so, we highlight the use of nonpharmacologic interventions as a potential strategy for improving clinical outcomes in chronic inflammatory conditions such as RA.