Winthrop Kevin L
Division of Infectious Diseases, Department of Medicine, Oregon Health and Science University, Portland, OR 97239-4197, USA.
Nat Clin Pract Rheumatol. 2006 Nov;2(11):602-10. doi: 10.1038/ncprheum0336.
Tumor necrosis factor (TNF) is a proinflammatory cytokine that has a key role in the pathogenesis of a variety of autoimmune diseases-including rheumatoid arthritis-and is an important constituent of the human immune response to infection. At present, three anti-TNF agents are approved (in the US and elsewhere) to treat selected autoimmune diseases: infliximab, etanercept, and adalimumab. These biologic agents have been associated with a variety of serious and 'routine' opportunistic infections; however, differences exist in the mechanisms of action of these agents that might confer variation in their associated risks of infection. From a public-health standpoint, the development of active tuberculosis in some patients who receive anti-TNF therapy is a matter of serious concern. Tuberculosis in such patients frequently presents as extrapulmonary or disseminated disease, and clinicians should be vigilant for tuberculosis in any patient taking anti-TNF therapy who develops fever, weight loss, or cough. To prevent the reactivation of latent tuberculosis infection during anti-TNF therapy, clinicians should screen all patients for tuberculosis, and begin treatment if latent infection is found, before anti-TNF therapy is initiated. Specific tuberculosis screening and treatment strategies vary between geographical regions and are reviewed in this document. The screening strategies employed in Europe and North America have reduced the occurrence of anti-TNF-associated tuberculosis and are clearly to be recommended, but the role of screening in the prevention of other opportunistic (e.g. fungal) infections is far less certain.
肿瘤坏死因子（TNF）是一种促炎细胞因子，在包括类风湿关节炎在内的多种自身免疫性疾病的发病机制中起关键作用，并且是人体对感染免疫反应的重要组成部分。目前，三种抗TNF药物（在美国及其他地区）已被批准用于治疗特定的自身免疫性疾病：英夫利昔单抗、依那西普和阿达木单抗。这些生物制剂与多种严重和“常见”的机会性感染相关；然而，这些药物的作用机制存在差异，这可能导致其相关感染风险有所不同。从公共卫生的角度来看，一些接受抗TNF治疗的患者发生活动性结核病是一个严重关切的问题。此类患者的结核病常表现为肺外或播散性疾病，临床医生应对任何接受抗TNF治疗且出现发热、体重减轻或咳嗽的患者保持警惕，以防结核病。为防止抗TNF治疗期间潜伏性结核感染的重新激活，临床医生应在开始抗TNF治疗前对所有患者进行结核病筛查，如发现潜伏感染则开始治疗。不同地理区域的具体结核病筛查和治疗策略有所不同，本文对此进行了综述。欧洲和北美的筛查策略已减少了抗TNF相关结核病的发生，显然值得推荐，但筛查在预防其他机会性（如真菌）感染方面的作用则远不那么确定。
