Department of Internal Medicine, University of Genova, Italy.
Clin Exp Rheumatol. 2011 Sep-Oct;29(5 Suppl 68):S-19-22. Epub 2011 Oct 21.
The central nervous biological CLOCK system (highly conserved and sophisticated molecular 'clock'), under the influence of light/dark alterations, 'creates' the internal circadian rhythms. The organisms 'feel' these rhythmic external changes to synchronise their physical activities, including energy metabolism, sleep, and immune function. A number of immunological functions are dependent on influence of sleep on circadian rhythms, including the type and magnitude of immune responses following antigenic challenge. Loss of sleep, in turn, prevents these immunosupportive actions and alters the production of glucocorticoids during the night. Major life events lead to an intense release of stress response system mediators (mainly norepinephrine and cortisol), whereas in minor life events, only short-lived surges of these neurotransmitters and hormones are expected. The immune system reactivity follows circadian rhythms imposed by the CLOCK and sleep synchronisation, and is particularly altered in presence of chronic stress. As a consequence of the altered CNS-endocrine control, low-dose long-term glucocorticoid therapy in chronic rheumatic diseases is today considered as a 'hormonal replacement therapy' to supplement the peripheral insufficiency of endogenous glucocorticoids in modulating the immune/inflammatory reaction.
中枢神经生物学时钟系统（高度保守且复杂的分子“时钟”）在光/暗变化的影响下“创造”了内部的昼夜节律。生物体“感知”这些有节奏的外部变化，以协调它们的身体活动，包括能量代谢、睡眠和免疫功能。许多免疫学功能依赖于睡眠对昼夜节律的影响，包括抗原挑战后免疫反应的类型和强度。反过来，睡眠不足会阻止这些免疫支持作用，并改变夜间糖皮质激素的产生。重大生活事件会导致应激反应系统介质（主要是去甲肾上腺素和皮质醇）的强烈释放，而在较小的生活事件中，这些神经递质和激素只会出现短暂的激增。免疫系统反应遵循时钟和睡眠同步产生的昼夜节律，如果存在慢性应激，这种节律会特别改变。由于中枢神经系统-内分泌控制的改变，在慢性风湿性疾病中，低剂量长期糖皮质激素治疗目前被认为是一种“激素替代疗法”，以补充内源性糖皮质激素在外周调节免疫/炎症反应方面的不足。
