Boumpas D T, Chrousos G P, Wilder R L, Cupps T R, Balow J E
National Institutes of Health, Bethesda, MD 20892.
Ann Intern Med. 1993 Dec 15;119(12):1198-208. doi: 10.7326/0003-4819-119-12-199312150-00007.
Glucocorticoids are pleiotropic hormones that at pharmacologic doses prevent or suppress inflammation and other immunologically mediated processes. At the molecular level, glucocorticoids form complexes with specific receptors that migrate to the nucleus where they interact with selective regulatory sites within DNA; this results in positive and negative modulation of several genes involved in inflammatory and immune responses. At the cellular level, glucocorticoids inhibit the access of leukocytes to inflammatory sites; interfere with the functions of leukocytes, endothelial cells, and fibroblasts; and suppress the production and the effects of humoral factors involved in the inflammatory response. Clinically, several modes of glucocorticoid administration are used, depending on the disease process, the organ involved, and the extent of involvement. High doses of daily glucocorticoids are usually required in patients with severe diseases involving major organs, whereas alternate-day regimens may be used in patients with less aggressive diseases. Intravenous glucocorticoids (pulse therapy) are frequently used to initiate therapy in patients with rapidly progressive, immunologically mediated diseases. The benefits of glucocorticoid therapy can easily be offset by severe side effects; even with the greatest care, side effects may occur. Moreover, for certain complications (for example, infection diathesis, peptic ulcer, osteoporosis, avascular necrosis, and atherosclerosis), other drug toxicities and pathogenic factors overlap with glucocorticoid effects. Minimizing the incidence and severity of glucocorticoid-related side effects requires carefully decreasing the dose; using adjunctive disease-modifying immunosuppressive and anti-inflammatory agents; and taking general preventive measures.
糖皮质激素是具有多种作用的激素，在药理剂量下可预防或抑制炎症及其他免疫介导过程。在分子水平上，糖皮质激素与特定受体形成复合物，这些复合物迁移至细胞核并与DNA内的选择性调控位点相互作用；这导致参与炎症和免疫反应的多个基因受到正向和负向调节。在细胞水平上，糖皮质激素抑制白细胞进入炎症部位；干扰白细胞、内皮细胞和成纤维细胞的功能；并抑制参与炎症反应的体液因子的产生及其作用。临床上，根据疾病进程、受累器官及受累程度，使用多种糖皮质激素给药方式。涉及主要器官的严重疾病患者通常需要大剂量每日使用糖皮质激素，而病情较轻的疾病患者可采用隔日疗法。静脉注射糖皮质激素（冲击疗法）常用于快速进展的免疫介导疾病患者的初始治疗。糖皮质激素治疗的益处很容易被严重的副作用抵消；即使极为小心，也可能出现副作用。此外，对于某些并发症（如感染倾向、消化性溃疡、骨质疏松、缺血性坏死和动脉粥样硬化），其他药物毒性和致病因素与糖皮质激素的作用相互重叠。尽量减少糖皮质激素相关副作用的发生率和严重程度需要谨慎降低剂量；使用辅助性改善病情的免疫抑制和抗炎药物；并采取一般预防措施。
