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关注:影响皮肤科治疗药物的生物制剂。

Focus on: biologics that affect therapeutic agents in dermatology.

作者信息

Saripalli Yamini V, Gaspari Anthony A

机构信息

Department of Dermatology, University of Maryland, Baltimore, MD 21201-1734, USA.

出版信息

J Drugs Dermatol. 2005 Mar-Apr;4(2):233-45.

Abstract

Tumor necrosis factor (TNF)-alpha is one of the oldest known cytokines in human physiology. It is involved in both normal and pathologic states. Virtually every cell and organ in the body are affected by TNF-alpha. Though TNF-alpha is usually involved in inflammation as a normal host defense response, when overproduced, it can become pathologic and affect almost every organ system. In this article, we address the role of TNF-alpha in diseases such as rheumatoid arthritis, Crohn's disease, psoriasis, and ankylosing spondylitis as well as the drugs used to modulate TNF-alpha. Specifically, we look at the structure, mechanism of action, and clinical use for etanercept, infliximab, and adalimumab. Historically, we also review the drug lenercept, another TNF-alpha modulator. These drugs offer alternative effective treatments to rheumatologic and dermatologic diseases without as many of the toxic side effects of some of the traditional therapies. The traditional agents target TNF-alpha in addition to several other modes of action (disease modifying anti-rheumatic drugs [DMARDS] such as cyclosporine and methotrexate) (Table 1). Though TNF-alpha immunomodulation seems to be a very effective, promising treatment in several TNF-alpha mediated disease processes, long-term studies need to be performed to assess the risk-benefit ratio of using these drugs over an extended period of time.

摘要

肿瘤坏死因子(TNF)-α是人类生理学中已知最古老的细胞因子之一。它参与正常和病理状态。身体几乎每个细胞和器官都受TNF-α影响。虽然TNF-α通常作为正常宿主防御反应参与炎症,但过量产生时,它会变得病理性并影响几乎每个器官系统。在本文中,我们阐述TNF-α在类风湿性关节炎、克罗恩病、银屑病和强直性脊柱炎等疾病中的作用以及用于调节TNF-α的药物。具体而言,我们研究依那西普、英夫利昔单抗和阿达木单抗的结构、作用机制及临床应用。从历史角度看,我们还回顾了另一种TNF-α调节剂药物来那西普。这些药物为风湿性和皮肤病提供了有效的替代治疗方法,且没有一些传统疗法那么多的毒副作用。传统药物除了几种其他作用方式(如环孢素和甲氨蝶呤等改善病情抗风湿药[DMARDs])外还靶向TNF-α(表1)。尽管TNF-α免疫调节在几种TNF-α介导的疾病过程中似乎是一种非常有效且有前景的治疗方法,但需要进行长期研究以评估长期使用这些药物的风险效益比。

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