Institute of Biochemical Pharmacology, Medical University of Innsbruck, Peter Mayr Str. 1, 6020 Innsbruck, Austria.
Biomolecules. 2021 Aug 30;11(9):1291. doi: 10.3390/biom11091291.
Inflammatory arthritis is a cluster of diseases caused by unregulated activity of the immune system. The lost homeostasis is followed by the immune attack of one's self, what damages healthy cells and tissues and leads to chronic inflammation of various tissues and organs (e.g., joints, lungs, heart, eyes). Different medications to control the excessive immune response are in use, however, drug resistances, flare-reactions and adverse effects to the current therapies are common in the affected patients. Thus, it is essential to broaden the spectrum of alternative treatments and to develop disease-modifying drugs. In the last 20 years, the involvement of the innate immune receptors TLRs in inflammatory arthritis has been widely investigated and targeting either the receptor itself or the proteins in the downstream signalling cascades has emerged as a promising therapeutic strategy. Yet, concerns about the use of pharmacological agents that inhibit TLR activity and may leave the host unprotected against invading pathogens and toxicity issues amid inhibition of downstream kinases crucial in various cellular functions have arisen. This review summarizes the existing knowledge on the role of TLRs in inflammatory arthritis; in addition, the likely druggable related targets and the developed inhibitors, and discusses the pros and cons of their potential clinical use.
炎症性关节炎是一组由免疫系统失调引起的疾病。失去的体内平衡随后会导致自身的免疫攻击，损害健康细胞和组织，并导致各种组织和器官（如关节、肺、心脏、眼睛）的慢性炎症。目前有多种控制过度免疫反应的药物在使用，但在受影响的患者中，药物耐药性、爆发反应和对现有治疗方法的不良反应很常见。因此，扩大替代治疗方案的范围并开发疾病修饰药物至关重要。在过去的 20 年中，人们广泛研究了先天免疫受体 TLR 在炎症性关节炎中的作用，针对受体本身或下游信号级联中的蛋白质的靶向治疗已成为一种很有前途的治疗策略。然而，人们对使用抑制 TLR 活性的药理制剂的担忧已经出现，因为这些制剂可能会使宿主无法抵御入侵的病原体，并且在抑制对各种细胞功能至关重要的下游激酶时会产生毒性问题。这篇综述总结了 TLR 在炎症性关节炎中的作用的现有知识；此外，还讨论了可能的可药物治疗的相关靶点和已开发的抑制剂，并讨论了它们在临床上的潜在应用的利弊。
