Baughman Robert P, Iannuzzi Michael
Interstitial Lung Disease and Sarcoidosis Clinic, University of Cincinnati Medical Center, Cincinnati, Ohio, USA.
BioDrugs. 2003;17(6):425-31. doi: 10.2165/00063030-200317060-00005.
Tumour necrosis factor (TNF)-alpha is a potent cytokine involved in the inflammatory reactions of many acute and chronic diseases. Recently, agents that block TNFalpha either directly or indirectly have been successful in the treatment of a variety of immune-mediated inflammatory disorders including rheumatoid arthritis and Crohn's disease. Sarcoidosis is an immune-mediated inflammatory disorder characterised by the formation of granulomas. TNFalpha is important in the initiation and perpetuation of inflammation in sarcoidosis, contributing to the initiation of granulomas and the progression of fibrosis, as well as to nongranulomatous inflammation. Various agents used to treat sarcoidosis affect TNF, including the most widely used drug class, corticosteroids, which are usually effective in blocking TNFalpha release from cells. Other agents that nonspecifically inhibit TNFalpha release include methotrexate, azathioprine and pentoxifylline. Specific TNF-antagonising biological agents such as infliximab and etanercept are being tested in patients with sarcoidosis, with mixed success. Infliximab has been shown to produce clinical improvement and reduce the requirement for corticosteroids in a small number of patients with sarcoidosis. However, as infliximab can be associated with reactivation of tuberculosis, which could be mistaken as worsening sarcoidosis, it should be used with caution in this patient group.
肿瘤坏死因子（TNF）-α是一种强效细胞因子，参与多种急慢性疾病的炎症反应。最近，直接或间接阻断TNFα的药物已成功用于治疗包括类风湿性关节炎和克罗恩病在内的多种免疫介导的炎症性疾病。结节病是一种以肉芽肿形成为特征的免疫介导的炎症性疾病。TNFα在结节病炎症的起始和持续过程中起重要作用，有助于肉芽肿的形成和纤维化的进展，以及非肉芽肿性炎症。用于治疗结节病的各种药物都会影响TNF，包括最常用的药物类别——皮质类固醇，其通常能有效阻断细胞释放TNFα。其他非特异性抑制TNFα释放的药物包括甲氨蝶呤、硫唑嘌呤和己酮可可碱。特异性TNF拮抗生物制剂如英夫利昔单抗和依那西普正在结节病患者中进行试验，效果不一。已证明英夫利昔单抗可使少数结节病患者临床症状改善并减少皮质类固醇的用量。然而，由于英夫利昔单抗可能与结核病复发有关，而这可能被误诊为结节病恶化，因此在该患者群体中应谨慎使用。
