Anti-cytokine therapeutics and infections
Anti-cytokine therapeutics and infections
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DOI：
10.1016/s0264-410x(03)00196-8
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发表时间：
2003-06-01
期刊：
影响因子：
5.5
通讯作者：
Dinarello, CA
中科院分区：
文献类型：
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作者：
Dinarello, CA
鉴于抗细胞因子治疗自身免疫性疾病的使用日益增多，特异性细胞因子在宿主抵抗感染中的作用已成为一个高度相关的研究领域。全世界有30多万名患者正在接受药物治疗，这些药物专门阻断白介素1(IL-1)或肿瘤坏死因子(TNF)的生物活性，以减轻类风湿性关节炎、克罗恩病或牛皮癣等自身免疫性疾病的严重程度。那些接受抗肿瘤坏死因子-α或IL-1阻断治疗的患者是在慢性基础上进行治疗的。研究表明，其他慢性炎症性疾病将受益于抗细胞因子治疗。然而，越来越多的临床证据表明，中和肿瘤坏死因子-α与机会性感染(包括分枝杆菌疾病)的风险增加有关。目前，用IL-1受体拮抗剂(IL-1ra)阻断IL-1活性似乎是相对安全的。然而，由于医生报告不足(一些估计报告的感染不到这些感染的5%)，严重和非严重感染的真实发病率仍将未知。与基于细胞因子的抗治疗相关的感染增加是否令人惊讶？在宿主防御的两个组成部分，先天反应和后天反应中，哪些会受到抗细胞因子治疗的影响？从大量使用活体感染模型进行的啮齿动物研究中，可以得出以下结论：(1)在革兰氏阳性或革兰氏阴性活菌感染模型中，肿瘤坏死因子-α的中和或基因缺失往往与宿主防御能力降低有关；(2)白介素1受体的缺失也会导致对李斯特菌或革兰氏阳性菌的抵抗力降低；(3)在对抗结核分枝杆菌引起的感染的防御中，需要肿瘤坏死因子-α和干扰素-γ。(C)2003爱思唯尔科学有限公司。保留所有权利。
In view of the increasing use of anti-cytokine-based therapies to treat autoimmune diseases, the role of specific cytokines in host defense against infection has become a highly relevant area of investigation. There are over 300,000 patients worldwide being treated with agents that specifically block the biological activities of interleukin-1 (IL-1) or tumor necrosis factor (TNF) for reducing the severity of autoimmune diseases such as rheumatoid arthritis, Crohn's disease or psoriasis. Those patients receiving anti-TNF-alpha or IL-1 blocking therapies are treated on a chronic basis. Studies suggest that other chronic inflammatory diseases will benefit from anti-cytokine therapies. However, there is a growing body of clinical evidence that neutralization of TNF-alpha is associated with an increased risk of opportunistic infections, including mycobacterial diseases. Blockade of IL-1 activity with the IL-1 receptor antagonist (IL-1Ra) appears, at present, to be relatively safe. However, because of physician under reporting (some estimates of reporting being less than 5% of these infections), the true incidence of infections, both serious and non-serious, will remain unknown. Does the increase in infections associated with anti-cytokine-based therapies come as a surprise? Of the two components of host defense, the innate and the acquired responses, which are affected by anti-cytokine therapies? From a wealth of rodent studies using live infection models, the following conclusions can be drawn: (1) neutralization or gene deletion for TNF-alpha is frequently associated with reduction of host defense in models of live Gram-positive or Gram-negative infections as well as infection by intracellular microbes such as Salmonella and Listeria; (2) absence of the IL-1 receptor can also result in decreased resistance to Listeria or Gram-positive bacteria and (3) TNF-alpha and IFN-gamma are required for defense against infection caused by Mycobacterium tuberculosis. (C) 2003 Elsevier Science Ltd. All rights reserved.