Effects of three anti-TNF-α drugs:: Etanercept, infliximab and pirfenidone on release of TNF-α in medium and TNF-a associated with the cell in vitro
Effects of three anti-TNF-α drugs:: Etanercept, infliximab and pirfenidone on release of TNF-α in medium and TNF-a associated with the cell in vitro
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DOI：
10.1016/j.intimp.2008.01.013
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发表时间：
2008-05-01
影响因子：
5.6
通讯作者：
Margolin, S. B.
中科院分区：
文献类型：
--
作者：
Grattendick, K. J.;Nakashima, J. M.;Margolin, S. B.
肿瘤坏死因子-α（TNF-α）是炎症过程的重要组成部分，其异常过度表达与许多疾病状态有关。新的治疗策略已经寻求减少循环TNF-α，使用中和抗TNF-α结合蛋白如依那西普或通过抑制新生TNF-α合成的药物如吡非尼酮。在本研究中，我们研究了两类药物对THP-1细胞分泌和细胞相关TNF-α的影响。如通过生物测定所测量的，所有测试的药物在用LPS刺激后显著降低生物活性TNF-α的分泌水平。然而，依那西普处理的细胞与细胞相关的TNF-α的水平比单独的LPS处理组高约6倍。令人惊讶的是，LPS+英夫利昔单抗处理的细胞相对于单独的LPS处理没有增加细胞相关的TNF-α。吡非尼酮显著降低分泌的和细胞相关的TNF-α水平。细胞相关TNF-α的这些药物相关差异可能在未来对抗TNF-α药物在TNF-α疾病管理中的治疗用途具有广泛的意义。(c)2008 Elsevier B. V.保留所有权利。
Tumor necrosis factor-alpha (TNF-alpha) is a vital component of the inflammatory process and its aberrant over-expression has been linked to numerous disease states. New treatment strategies have sought to reduce circulating TNF-a, either with neutralizing anti-TNF-alpha binding proteins such as etanercept or via drugs that inhibit de nova TNF-a synthesis like pirfenidone. In the present study, we examined the effects of both classes of drugs on secreted and cell-associated TNF-a produced by THP-1 cells. All of the tested drugs significantly reduced secreted levels of bioactive TNF-a following stimulation with LPS as measured by bioassay. However, etanercept-treated cells had approximately six-fold higher levels of cell-associated TNF-a compared with that of the LPS-alone treatment group. Surprisingly, LPS+infliximab treated cells did not increase cell-associated TNF-a relative to the LPS-alone treatment. Pirfenidone significantly reduced both secreted and cell-associated TNF-a Levels. These drug-related differences in cell-associated TNF-a may have broad implications in the future for the therapeutic uses of anti-TNF-alpha drugs in the management of TNF-a diseases. (c) 2008 Elsevier B.V. All rights reserved.