Division of Rheumatology, Department of Medicine III, University Clinical Center Carl Gustav Carus at the Technical University of Dresden, Germany.
Autoimmun Rev. 2012 Mar;11(5):321-5. doi: 10.1016/j.autrev.2011.05.001. Epub 2011 May 18.
TNF is an important mediator of inflammation, but is also involved in the control of autoimmunity. The latter has been demonstrated in a murine model of SLE (NZB/W) and by the occurrence of autoantibodies to nuclear antigens as well as occasional, transient lupus-like syndromes in patients under TNF blockade. In contrast, data on increased TNF levels in serum, kidney and skin samples of SLE patients as well as results in other mouse models of the disease point to an inflammatory role of TNF in SLE organ disease. Despite all due caution, given these two sides of the cytokine, TNF blockade has by now been employed for several years in single cases and open label studies; data on more than fifty patients have meanwhile been published, for the vast majority of which infliximab was employed. These clinical data have to be very cautiously interpreted, as always with data on single cases or open label trials. However, some consistent pieces of information emerge and may inform controlled clinical trials: (i) While antibodies to double-stranded DNA commonly showed transient increases, lupus flares have not been seen so far and thus apparently are at least not the rule; (ii) in contrast, increases in anti-phospholipid antibodies may be associated with vascular adverse events; (iii) bacterial infections, pneumonia and urinary tract infections in particular, have been observed; (iv) short term induction therapy appears relatively safe, while long-term TNF blockade may confer significant risks in SLE; (v) TNF blocker induction therapy may lead to long-term remission in patients with lupus nephritis, hemophagocytic syndrome, and interstitial lung disease; (vi) patients with lupus arthritis often respond to TNF-blockade but symptoms recur after cessation of therapy, necessitating longer term therapy, which is more risky than short term treatment.
TNF 是炎症的重要介质，但也参与自身免疫的控制。后者在 SLE 的鼠模型（NZB/W）中得到了证实，并且在 TNF 阻断的患者中也发生了针对核抗原的自身抗体以及偶尔出现的、短暂的狼疮样综合征。相比之下，SLE 患者血清、肾脏和皮肤样本中 TNF 水平升高的相关数据以及其他疾病的小鼠模型的结果表明，TNF 在 SLE 器官疾病中具有炎症作用。尽管有这些注意事项，但鉴于细胞因子的这两个方面，TNF 阻断剂现已在个别病例和开放标签研究中使用了数年；目前已经发表了 50 多个患者的数据，其中绝大多数患者使用了英夫利昔单抗。这些临床数据必须非常谨慎地解释，就像单个病例或开放标签试验的数据一样。然而，一些一致的信息已经出现，并可能为对照临床试验提供信息：（i）虽然抗双链 DNA 抗体通常会出现短暂的增加，但到目前为止还没有出现狼疮发作，因此显然至少不是常规情况；（ii）相反，抗磷脂抗体的增加可能与血管不良事件有关；（iii）已经观察到细菌感染、肺炎和尿路感染，特别是；（iv）短期诱导治疗似乎相对安全，而长期 TNF 阻断可能会给 SLE 患者带来重大风险；（v）TNF 阻滞剂诱导治疗可能会导致狼疮肾炎、噬血细胞综合征和间质性肺病患者的长期缓解；（vi）狼疮关节炎患者通常对 TNF 阻断治疗有反应，但在停止治疗后症状会复发，需要长期治疗，这比短期治疗风险更大。
