Department of Pharmacology, Poona College of Pharmacy, Bharati Vidyapeeth Deemed University, Pune, India.
Department of Pharmacology, Sinhgad College of Pharmacy, Pune, India.
Immunopharmacol Immunotoxicol. 2020 Apr;42(2):59-73. doi: 10.1080/08923973.2020.1728765. Epub 2020 Feb 18.
Inflammation is a physiological intrinsic host response to injury meant for removal of noxious stimuli and maintenance of homeostasis. It is a defensive body mechanism that involves immune cells, blood vessels and molecular mediators of inflammation. Glucocorticoids (GCs) are steroidal hormones responsible for regulation of homeostatic and metabolic functions of body. Synthetic GCs are the most useful anti-inflammatory drugs used for the treatment of chronic inflammatory diseases such as asthma, chronic obstructive pulmonary disease (COPD), allergies, multiple sclerosis, tendinitis, lupus, atopic dermatitis, ulcerative colitis, rheumatoid arthritis and osteoarthritis whereas, the long term use of GCs are associated with many side effects. The anti-inflammatory and immunosuppressive (desired) effects of GCs are usually mediated by transrepression mechanism whereas; the metabolic and toxic (undesired) effects are usually manifested by transactivation mechanism. Though GCs are most potent anti-inflammatory and immunosuppressive drugs, the common problem associated with their use is GC resistance. Several research studies are rising to comprehend these mechanisms, which would be helpful in improving the GC resistance in asthma and COPD patients. This review aims to focus on identification of new drug targets in inflammation which will be helpful in the resolution of inflammation. The ample understanding of GC mechanisms of action helps in the development of novel anti-inflammatory drugs for the treatment of inflammatory and autoimmune disease with reduced side effects and minimal toxicity.
炎症是一种生理性的固有宿主反应，旨在消除有害刺激并维持体内平衡。它是一种涉及免疫细胞、血管和炎症分子介质的防御机制。糖皮质激素（GCs）是负责调节身体内稳态和代谢功能的甾体激素。合成 GCs 是治疗哮喘、慢性阻塞性肺疾病（COPD）、过敏、多发性硬化症、肌腱炎、狼疮、特应性皮炎、溃疡性结肠炎、类风湿关节炎和骨关节炎等慢性炎症性疾病最有用的抗炎药物，而 GCs 的长期使用与许多副作用有关。GCs 的抗炎和免疫抑制（所需）作用通常通过反式抑制机制介导，而代谢和毒性（不需要）作用通常通过反式激活机制表现出来。尽管 GCs 是最有效的抗炎和免疫抑制剂，但与它们的使用相关的常见问题是 GC 耐药性。许多研究正在兴起，以了解这些机制，这将有助于改善哮喘和 COPD 患者的 GC 耐药性。本综述旨在重点关注炎症中新的药物靶点的鉴定，这将有助于炎症的解决。对 GC 作用机制的充分理解有助于开发新型抗炎药物，用于治疗炎症和自身免疫性疾病，减少副作用和最小毒性。
