Institute of Neurobiology, Center of Brain, Behavior and Metabolism, University of Lübeck, Marie Curie Street, 23563, Lübeck, Germany.
NIHR Oxford Biomedical Research Centre, John Radcliffe Hospital, Oxford, OX3 9DU, UK.
Semin Immunopathol. 2022 Mar;44(2):153-163. doi: 10.1007/s00281-021-00889-2. Epub 2021 Sep 28.
Adrenal glucocorticoid (GC) hormones are important regulators of energy metabolism, brain functions, and the immune system. Their release follows robust diurnal rhythms and GCs themselves serve as entrainment signals for circadian clocks in various tissues. In the clinics, synthetic GC analogues are widely used as immunosuppressive drugs. GC inhibitory effects on the immune system are well documented and include suppression of cytokines and increased immune cell death. However, the circadian dynamics of GC action are often neglected. Synthetic GC medications fail to mimic complex GC natural rhythms. Several recent publications have shown that endogenous GCs and their daily concentration rhythms prepare the immune system to face anticipated environmental threats. That includes migration patterns that direct specific cell population to organs and tissues best exemplified by the rhythmic expression of chemoattractants and their receptors. On the other hand, chronotherapeutic approaches may benefit the treatment of immunological diseases such as asthma. In this review, we summarise our current knowledge on the circadian regulation of GCs, their role in innate and adaptive immune functions and the implications for the clinics.
肾上腺糖皮质激素(GC)是能量代谢、大脑功能和免疫系统的重要调节剂。它们的释放遵循强大的昼夜节律,GC 本身就是各种组织中生物钟的授时信号。在临床上,合成 GC 类似物被广泛用作免疫抑制剂。GC 对免疫系统的抑制作用已有充分的记录,包括抑制细胞因子和增加免疫细胞死亡。然而,GC 作用的昼夜动态往往被忽视。合成 GC 药物无法模拟复杂的 GC 自然节律。最近的几项出版物表明,内源性 GC 及其每日浓度节律使免疫系统能够应对预期的环境威胁。这包括引导特定细胞群迁移到器官和组织的模式,以趋化因子及其受体的节律性表达为例。另一方面,时间治疗方法可能有益于治疗哮喘等免疫性疾病。在这篇综述中,我们总结了我们目前对 GC 的昼夜调节、它们在先天和适应性免疫功能中的作用以及对临床的影响的认识。