Haider Asifa S, Cardinale Irma R, Whynot Julia A, Krueger James G
Laboratory of Investigative Dermatology, Rockefeller University, New York, New York 10021, USA.
J Investig Dermatol Symp Proc. 2007 May;12(1):9-15. doi: 10.1038/sj.jidsymp.5650032.
Proinflammatory diseases like rheumatoid arthritis, Crohn's disease, and psoriasis have been treated by the tumor necrosis factor (TNF) antagonists infliximab and etanercept with different degrees of success. Although these agents are widely used in humans, little is known about their mechanisms of action or why etanercept and infliximab have differences in clinical activity. In this study, we define leukocyte genes that are suppressed by etanercept within 24 hours of exposure. Compared to previous work with infliximab, fewer immune-related genes are suppressed by etanercept. Importantly, the range of genes suppressed by these alternative TNF inhibitors is only partially overlapping, suggesting each has unique immune modulating effects. In sharp contrast to etanercept, infliximab strongly suppresses genes associated with "Type 1" immune responses (IFN-gamma and the IL-12-receptor beta 2 subunit), providing a clear mechanism for clinically relevant immune suppression.
类风湿性关节炎、克罗恩病和牛皮癣等促炎性疾病已通过肿瘤坏死因子（TNF）拮抗剂英夫利昔单抗和依那西普进行治疗，取得了不同程度的成功。尽管这些药物在人类中广泛使用，但对其作用机制或依那西普和英夫利昔单抗临床活性存在差异的原因知之甚少。在本研究中，我们确定了依那西普在暴露24小时内抑制的白细胞基因。与之前使用英夫利昔单抗的研究相比，依那西普抑制的免疫相关基因较少。重要的是，这些替代性TNF抑制剂抑制的基因范围只是部分重叠，表明每种药物都有独特的免疫调节作用。与依那西普形成鲜明对比的是，英夫利昔单抗强烈抑制与“1型”免疫反应相关的基因（干扰素-γ和白细胞介素-12受体β2亚基），为临床上相关的免疫抑制提供了明确的机制。
