ANTI TNF ALPHA ACTIVITY OF THALIDOMIDE IN TNF ALPHA ARTHRITIS

描述（改编自申请）：药物沙利度胺是 在20世纪60年代经常被用作早晨的镇静剂 疾病，但其使用由于Tetratogenicity停止。然而，在这方面， 这种药剂的非镇静剂 和非胚胎作用，即其免疫调节活性。 沙利度胺是一种抗肿瘤坏死因子α的药物， 被描述为有效治疗自身免疫性疾病 例如麻风病，治疗艾滋病毒注射引起的疾病， 口疮性溃疡和恶病质，以及HIV-1的抑制 复制和艾滋病进展。一些研究人员描述了 这种潜在重要的免疫调节作用的矛盾 治疗方法尚不清楚。因此，建议研究的重点 是为了确定沙利度胺在正常C57 BL/6小鼠中的作用， hTNF-α转基因C57 BL/6小鼠。这些假设的提出 一系列实验表明，沙利度胺的抗TNF α活性 介导免疫调节作用，并将改变免疫系统的功能。 免疫系统在细胞水平。拟议研究的目的 包括：（1）确定使用沙利度胺的任何副作用 在正常小鼠模型中;（2）观察并确定沙利度胺是否 诱导关节炎易感hTNF-α的症状显著缓解， α转基因小鼠;（3）确定沙利度胺是否改变了 正常人和转基因人T和β淋巴细胞免疫活性 评价沙利度胺对小鼠白细胞-细胞增殖的影响 相互作用和程序性细胞死亡和凋亡。生成的数据 从拟议的研究将提供有关行动的重要信息 在细胞水平上的反应。此外，这些实验 将允许观察该药物对动物的活性 一种最常见的人类自身免疫性疾病关节炎的模型。 最后，阐明了这种抗TNF-α的方法， 该制剂可用于治疗其他自身免疫性疾病， 疾病和艾滋病毒/艾滋病。

Description (Adapted from Application): The drug thalidomide was frequently administered in the 1960's as a sedative for morning sickness, but its use was discontinued due to tetratogenicity. However, this agent has experienced a resurgence in interest in its non-sedative and non-embryonic effects, namely its immunomodulatory activity. Thalidomide, an anti-tumor necrosis factor alpha agent, has been described as being effective in the treatment of autoimmune disorders such as leprosy, the treatment of disorders due to HIV injection such as aphthous ulcerations and cachexia, and the inhibition of HIV-1 replication and AIDS progression. Several researchers have described contradictory immunomodulatory effects of this potentially important therapeutic is still unclear. Therefore, the focus of the proposed study is to determine the effects of thalidomide in normal C57BL/6 mice and hTNF-alpha transgenic C57BL/6 mice. The hypothesis of these proposed series of experiments is that the anti-TNF alpha activity of thalidomide mediates the immunomodulatory effects and will alter the function of the immune system at the cellular level. The aims of the proposed study include: (1) to determine any side effects to the use of the thalidomide in a normal murine model; (2) to observe and determine if thalidomide induces a significant alleviation of symptoms in arthritis-prone hTNF- alpha transgenic mice; (3) to determine if thalidomide alters the immunocompetence of T and beta lymphocytes in normal and transgenic mice; and (4) to assess the effect of thalidomide on leukocyte cell-cell interactions and programmed cell death and apoptosis. The data generated from the proposed study will supply important information on the action of thalidomide at the cellular level. Additionally, these experiments will allow the observation of the activity of this drug on an animal model for one the most common human autoimmune diseases, arthritis. Finally, the elucidation of the method by which this anti-TNF-alpha agent works may be applied to the treatment of other autoimmune disorders and HIV/AIDS diseases.