Chronobiology and Chronotherapy in Inflammatory Joint Diseases

Abstract

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.

Circadian Modulation of the Antioxidant Effect of Grape Consumption: A Randomized Controlled Trial

“…Support for pursuing the investigation of timed bioactive food consumption is provided by chronotherapy studies showing improved effectiveness of glucocorticoids in patients with rheumatoid arthritis when administered to target peak times of cytokine release and symptom severity [57][58][59]68,69]. Further, compared to non-timed therapy for anti-hypertensive medications, long-term chronotherapy reduces the risk of comorbidities such as cardiovascular and kidney disease [70,71].…”

Biological rhythms and epilepsy treatment

“…Chronopharmacology could offer personalized treatment tailored to individual variations in seizure activity, pharmacokinetics, and pharmacodynamics. Similar therapy is being established in various clinical contexts, like cancer treatment ( 38 ), rheumatology ( 39 ), and antihypertensive treatment ( 40 ).…”

Expression Patterns of Clock Gene mRNAs and Clock Proteins in Human Psoriatic Skin Samples

“…It is a treatment approach whereby the goal is to optimize the efficacy of treatment and minimize the adverse effects by taking into account the rhythm of the disease and the bioavailability of the treatment. As reviewed in recent articles, the timing and individually tailoring of medications (by adjusting to the person’s inner clock) is becoming increasingly important in inflammatory diseases or in cancer treatment [ 58 , 59 , 60 ].…”