脊椎关节病的anti-TNF治疗策略所存在的问题

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The problem with treating spondylarthritis with anti-TNF strategies
治疗(脊)椎关节炎时抗－TNF策略存在的问题
Joint fusion and joint inflammation are separate processes, study suggests, and should be considered separate therapeutic targets
研究显示关节融合术和关节感染是各自独立的过程，在治疗中应分别对待．
Any form of arthritis that affects one or more vertebral joints, spondylarthritis (SpA) represents a group of closely related disorders, including ankylosing spondylitis (AS), psoriatic arthritis (PsA), and arthritis associated with inflammatory bowel disease. 凡是影响一个或更多椎骨连结，(脊)椎关节的关节炎都显示出一组紧密相关的症状，包括强制性脊柱炎，银屑病关节炎和肠炎引起的关节炎．Aside from chronic inflammation, these conditions are all characterized by ankylosis, stiffness and fusion of bone in the spine and peripheral joints, provoked by abnormal cartilage and bone formation. 除去慢性炎症，当异常软骨和骨形成时，这些疾病都很表现出关节强直，四肢强直，脊柱和周围关节融合．What triggers ankylosis remains unknown. 引起关节强直的诱因还未找出．Currently, inhibition of tumor necrosis factor ?(TNF?) is the most effective strategy for controlling the painful symptoms of SpA and slowing vertebral joint destruction. But does anti-TNF therapy do anything to reduce the incidence or severity of ankylosis?关节强硬性脊椎炎和慢性椎关节破坏会引起疼痛，当前抑制肿瘤坏死因子是控制它们引起疼痛症状最有效的治疗．To answer this critical question, a quartet of researchers led by Dr. Frank P. Luyten, Division of Rheumatology, University Hospitals, Leuven, Belgium, tested the effectiveness of etanercept, an established TNF receptor, on animal models of arthritis. 为了回答解决这个问题，由Frank P. Luyten 博士领导的四组研究员在动物关节炎模型上检测了依那西普的效果．Frank P. Luyten 博士在比利时列弗大学医院风湿病区就职．依那西普是一种已经证实的肿瘤坏死因子受体．Their findings, highlighted in the February 2007 issue of Arthritis & Rheumatism (http://www.interscience.wiley.com/journal/arthritis), cast doubts on the feasibility of preventing joint and spine ankylosis with anti-TNF strategies while shedding light on the process of SpA.他们的发现在2007年二月刊的《关节炎和风湿病》(http://www.interscience.wiley.com/journal/arthritis)上发表．当了解关节强硬性脊椎炎发病过程中，研究怀疑使用抗肿瘤坏死策略预防关节和脊柱关节强直的可行性．
A sample of male mice with spontaneous arthritis were caged together and observed from the age of 10 weeks. From week 12 to week 25, the mice were treated twice weekly with etanercept, in a strength comparable to standard dosage for human patients, or a placebo. 有特发关节炎的雄性小鼠样本关在一起，从十周开始观察．在十二周到二十五周期间，小鼠每周接受两次依那西普或安慰剂治疗，依那西普剂量与人类患者标准剂量相当．Mice were also scored twice weekly for signs of arthritis, including cartilage formation, bone formation, and joint ankylosis. The mice were killed at age 25 weeks, autopsied, and analyzed, through cell population staining, for the presence of TNF? 小鼠每周两次进行关节炎记分评估，记分根据关节炎体征，例如软骨结构，骨结构以及关节强直．小鼠在第二十五周处死，解剖，并分析．通过细胞种群染色来测定肿瘤坏死因子的存在情况．
In a complementary experiment, another sample of mice was induced with arthritis, using methylated bovine serum albumin. Four days later, these mice were given a single injection of etanercept. Three days later, on day seven, they were killed. Signs of arthritis were assessed and graded for cartilage destruction and bone erosion.
在补充实验中，另一组小鼠样本是使用甲基化牛血清白蛋白诱导形成关节炎．四天后，这些小鼠仅注射依那西普．三天后，在第七天，处死小鼠．评估关节炎体征，并根据软骨损害和骨侵蚀情况进行分级．
For the mice with induced arthritis, etanercept had a significant impact on disease severity, inhibiting inflammation and cartilage and bone destruction. For the mice with spontaneous arthritis, however, etanercept proved no more effective than placebo at inhibiting new cartilage or bone formation or ankylosis. What's more, TNF?positive cells were observed in the joint capsule, adjacent blood vessels and in new cartilage.
对诱导形成关节炎小鼠来说，在阻止疾病进展，抑制炎症，抑制软骨和骨损伤方面，依那西普有显著作用．对特发关节炎小鼠来说，在抑制新生软骨和骨形成或关节强直方面，依那西普与安慰剂没有显著区别．此外，肿瘤坏死因子阳性细胞在关节囊，邻近血管和新生软骨中发现．
\"Our observations strengthen our hypothesis that new bone formation in SpA is clinically relevant and largely independent of inflammation,\" Dr. Luyten states. \"Long-term results from clinical trials are required to corroborate this hypothesis in patients with SpA,\" he acknowledges, \"and to define whether the process of ankylosis should become a separate therapeutic target.\"
＂我们的观察支持我们的假设，在关节强硬性脊椎炎中新生骨形成与临床相关联，很大程度上不是由炎症引起的，＂Luyten陈述．＂来自临床实验的长期结果将在关节强硬性脊椎炎患者中验证这个假设．，＂他承认＂还要界定关节强直的过程是否会变成一个单独的治疗目标．＂