Muscari Isabella, Fierabracci Alessandra, Adorisio Sabrina, Moretti Marina, Cannarile Lorenza, Thi Minh Hong Vu, Ayroldi Emira, Delfino Domenico V
Section of Onco-hematology, Department of Medicine and Surgery, University of Perugia, Perugia, Italy.
Infectivology and Clinical Trials Research Department, Bambino Gesù Children's Hospital IRCCS, Rome, Italy.
Biochem Pharmacol. 2022 Apr;198:114930. doi: 10.1016/j.bcp.2022.114930. Epub 2022 Feb 9.
Glucocorticoids exert their pharmacological actions by mimicking and amplifying the function of the endogenous glucocorticoid system's canonical physiological stress response. They affect the immune system at the levels of inflammation and adaptive and innate immunity. These effects are the basis for therapeutic use of glucocorticoids. Innate immunity is the body's first line of defense against disease conditions. It is relatively nonspecific and, among its mediators, natural killer (NK) cells link innate and acquired immunity. NK cell numbers are altered in patients with auto immune diseases, and research suggests that interactions between glucocorticoids and natural killer cells are critical for successful glucocorticoid therapy. The aim of this review is to summarize these interactions while highlighting the latest and most important developments in this field. Production and release in the blood of endogenous glucocorticoids are strictly regulated by the hypothalamus-pituitary adrenal axis. A self-regulatory mechanism prevents excessive plasma levels of these hormones. However, exogenous stimuli such as stress, inflammation, infections, cancer, and autoimmune disease can trigger the hypothalamus-pituitary-adrenal axis response and lead to excessive systemic release of glucocorticoids. Thus, stress stimuli, such as sleep deprivation, intense exercise, depression, viral infections, and cancer, can result in release of glucocorticoids and associated immunosuppressant effects. Among these effects are decreases in the numbers and activities of NK cells in inflammatory and autoimmune diseases (e.g., giant cell arteritis, polymyalgia rheumatica, and familial hypogammaglobulinemia).
糖皮质激素通过模拟和放大内源性糖皮质激素系统典型生理应激反应的功能来发挥其药理作用。它们在炎症以及适应性免疫和固有免疫水平上影响免疫系统。这些作用是糖皮质激素治疗用途的基础。固有免疫是机体抵御疾病的第一道防线。它相对非特异性，在其介质中，自然杀伤（NK）细胞连接着固有免疫和获得性免疫。自身免疫性疾病患者的NK细胞数量会发生改变，并且研究表明糖皮质激素与自然杀伤细胞之间的相互作用对于糖皮质激素治疗的成功至关重要。本综述的目的是总结这些相互作用，同时突出该领域的最新且最重要的进展。内源性糖皮质激素在血液中的产生和释放受到下丘脑 - 垂体 - 肾上腺轴的严格调控。一种自我调节机制可防止这些激素在血浆中过度蓄积。然而，诸如应激、炎症、感染、癌症和自身免疫性疾病等外源性刺激可触发下丘脑 - 垂体 - 肾上腺轴反应，并导致糖皮质激素在全身过度释放。因此，诸如睡眠剥夺、剧烈运动、抑郁、病毒感染和癌症等应激刺激可导致糖皮质激素释放以及相关的免疫抑制作用。在这些作用中，炎症和自身免疫性疾病（如巨细胞动脉炎、风湿性多肌痛和家族性低丙种球蛋白血症）患者的NK细胞数量和活性会降低。
