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肿瘤坏死因子-α在佐剂诱导性关节炎中的矛盾效应。

Paradoxical effects of tumour necrosis factor-alpha in adjuvant-induced arthritis.

作者信息

Williams Richard O

出版信息

Arthritis Res Ther. 2008;10(3):113. doi: 10.1186/ar2430. Epub 2008 Jun 6.

DOI:10.1186/ar2430
PMID:18564403
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2483450/
Abstract

Anti-tumour necrosis factor (TNF)alpha therapy is highly effective in rheumatoid arthritis and it is surprising, therefore, that a recent study showed that intraperitoneal administration of recombinant TNFalpha reduced the severity of adjuvant-induced arthritis and decreased IFNgamma expression in cultured draining lymph node cells. Furthermore, in untreated arthritic rats, maximal TNFalpha expression in draining lymph node cells coincided with spontaneous disease remission, suggesting a role for endogenous TNFalpha in recovery from arthritis. If confirmed in further studies, these findings suggest that, in addition to its well-established pro-inflammatory properties, TNFalpha may also play a disease-limiting role in this model of rheumatoid arthritis by suppressing effector T cell responses.

摘要

抗肿瘤坏死因子（TNF）α疗法在类风湿性关节炎中具有高度疗效，因此，一项近期研究显示腹腔注射重组TNFα可减轻佐剂诱导性关节炎的严重程度，并降低培养的引流淋巴结细胞中的IFNγ表达，这令人惊讶。此外，在未经治疗的关节炎大鼠中，引流淋巴结细胞中TNFα的最大表达与自发性疾病缓解同时出现，提示内源性TNFα在关节炎恢复中发挥作用。如果在进一步研究中得到证实，这些发现表明，除了其已确立的促炎特性外，TNFα在这种类风湿性关节炎模型中可能还通过抑制效应T细胞反应发挥疾病限制作用。

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本文引用的文献

1
Exogenous tumour necrosis factor alpha induces suppression of autoimmune arthritis.外源性肿瘤坏死因子-α可诱导自身免疫性关节炎的抑制。
Arthritis Res Ther. 2008 Apr 1;10(1):R38. doi: 10.1186/ar2393.
2
Paradoxical anti-inflammatory actions of TNF-alpha: inhibition of IL-12 and IL-23 via TNF receptor 1 in macrophages and dendritic cells.肿瘤坏死因子-α的反常抗炎作用：通过巨噬细胞和树突状细胞中的肿瘤坏死因子受体1抑制白细胞介素-12和白细胞介素-23
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Evidence of radiographic benefit of treatment with infliximab plus methotrexate in rheumatoid arthritis patients who had no clinical improvement: a detailed subanalysis of data from the anti-tumor necrosis factor trial in rheumatoid arthritis with concomitant therapy study.在无临床改善的类风湿关节炎患者中，英夫利昔单抗联合甲氨蝶呤治疗的影像学获益证据：类风湿关节炎抗肿瘤坏死因子试验伴联合治疗研究数据的详细亚组分析
Arthritis Rheum. 2005 Apr;52(4):1020-30. doi: 10.1002/art.20982.
4
Lasker Clinical Medical Research Award. TNF defined as a therapeutic target for rheumatoid arthritis and other autoimmune diseases.拉斯克临床医学研究奖。肿瘤坏死因子被定义为类风湿性关节炎和其他自身免疫性疾病的治疗靶点。
Nat Med. 2003 Oct;9(10):1245-50. doi: 10.1038/nm939.
5
Exploring the reciprocal relationship between immunity and inflammation in chronic inflammatory arthritis.探索慢性炎症性关节炎中免疫与炎症之间的相互关系。
Rheumatology (Oxford). 2003 Jun;42(6):716-31. doi: 10.1093/rheumatology/keg262. Epub 2003 Mar 31.
6
A dual role for TNF-alpha in type 1 diabetes: islet-specific expression abrogates the ongoing autoimmune process when induced late but not early during pathogenesis.肿瘤坏死因子-α在1型糖尿病中的双重作用：胰岛特异性表达在发病机制后期而非早期诱导时可消除正在进行的自身免疫过程。
J Immunol. 2001 Jun 15;166(12):7023-32. doi: 10.4049/jimmunol.166.12.7023.
7
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J Immunol. 2000 Feb 15;164(4):1722-9. doi: 10.4049/jimmunol.164.4.1722.
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Neurology. 1999 Aug 11;53(3):457-65.