Ursini Francesco, De Giorgi Alfredo, D'Onghia Martina, De Giorgio Roberto, Fabbian Fabio, Manfredini Roberto
Medicine & Rheumatology Unit, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy.
Clinica Medica Unit, Department of Medical Sciences, University of Ferrara, via L. Borsari 47, 44121 Ferrara, Italy.
Pharmaceutics. 2021 Nov 2;13(11):1832. doi: 10.3390/pharmaceutics13111832.
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.
昼夜节律紊乱会影响包括自身免疫性疾病在内的多种病症的发展。本叙述性综述总结了目前对炎症性关节疾病中昼夜生物学的理解，并讨论了时间疗法的潜在应用。促炎细胞因子是类风湿关节炎（RA）发生和发展的关键因素，调节细胞存活/凋亡、分化和增殖。炎症细胞因子的产生和分泌表现出对人类昼夜周期的依赖性，导致细胞因子血浆水平在24小时内发生变化。此外，除了细胞因子分泌的昼夜节律外，RA中还存在计时机制的紊乱。考虑到时间疗法的概念，已引入缓释（MR）泼尼松片来抵消夜间促炎细胞因子峰值的负面影响。低剂量MR泼尼松似乎能够改善RA病程，减轻晨僵和降低早晨血清IL-6水平，并带来显著的临床益处。此外，据报道甲氨蝶呤（MTX）时间疗法与RA活动评分的显著改善有关。对于风湿性多肌痛和痛风也有类似的效果描述，尽管现有文献仍然有限。将生物钟学知识应用于炎症性关节疾病的不断增加，可能会刺激开发新的药物策略，以根据生物节律治疗患者并尽量减少副作用。
