Chronobiology and Chronotherapy in Inflammatory Joint Diseases

Circadian rhythm perturbations can impact the evolution of different conditions, including autoimmune diseases. This narrative review summarizes the current understanding of circadian biology in inflammatory joint diseases and discusses the potential application of chronotherapy. Proinflammatory cytokines are key players in the development and progression of rheumatoid arthritis (RA), regulating cell survival/apoptosis, differentiation, and proliferation. The production and secretion of inflammatory cytokines show a dependence on the human day-night cycle, resulting in changing cytokine plasma levels over 24 h. Moreover, beyond the circadian rhythm of cytokine secretion, disturbances in timekeeping mechanisms have been proposed in RA. Taking into consideration chronotherapy concepts, modified-release (MR) prednisone tablets have been introduced to counteract the negative effects of night-time peaks of proinflammatory cytokines. Low-dose MR prednisone seems to be able to improve the course of RA, reduce morning stiffness and morning serum levels of IL-6, and induce significant clinical benefits. Additionally, methotrexate (MTX) chronotherapy has been reported to be associated with a significant improvement in RA activity score. Similar effects have been described for polymyalgia rheumatica and gout, although the available literature is still limited. Growing knowledge of chronobiology applied to inflammatory joint diseases could stimulate the development of new drug strategies to treat patients in accordance with biological rhythms and minimize side effects.