Rheumatoid arthritis and Crohn's disease are costly diseases that result in significant long-term patient disability. They are chronic inflammatory diseases that are associated with increased production of Tumor Necrosis Factor (TNF). Blockage of this cytokine with bio-engineered compounds has significantly changed therapy of these diseases and has ushered in the era of biological therapy. The pro-inflammatory role of TNF is mediated by its essential respiratory burst function that is effectively inhibited by anti-TNF therapy. Anti-TNF therapy is effective in approximately two-thirds of patients to whom it is administered, but the effect is temporary. Lack of response to anti-TNF therapy stems from interplay of host-factors including: host cytokine response, disease phenotype, and antibody response to the anti-TNF agents. NOD 2, a defect present in approximately 50% of Crohn's disease patients, bears no relationship to non-response. Additionally, TNF promoter gene polymorphisms and TNF receptor gene heterogeneity play a significant role in non-response and disease course/severity. Adverse effects of anti-TNF therapy include early and delayed hypersensitivity reactions, cell-mediated infections, lupus-like syndrome, demyelinating diseases, and exacerbation of CHF.

中文翻译：

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TNF阻断的生物学作用。

类风湿关节炎和克罗恩氏病是昂贵的疾病，导致长期的严重患者残疾。它们是慢性炎性疾病，与肿瘤坏死因子（TNF）产生增加有关。用生物工程化合物对这种细胞因子的阻滞作用已大大改变了对这些疾病的治疗方法，并开创了生物治疗时代。TNF的促炎作用由其基本的呼吸爆发功能介导，该功能被抗TNF治疗有效抑制。抗TNF疗法在接受治疗的患者中大约三分之二有效，但这种效果是暂时的。对抗TNF治疗缺乏反应的原因在于宿主因素的相互作用，包括：宿主细胞因子反应，疾病表型和对抗TNF药物的抗体反应。2点 大约50％的克罗恩病患者中存在这种缺陷，与无反应无关。另外，TNF启动子基因多态性和TNF受体基因异质性在无应答和疾病进程/严重性中起重要作用。抗TNF疗法的不良反应包括早期和迟发型超敏反应，细胞介导的感染，狼疮样综合征，脱髓鞘疾病和CHF加重。