ANTI TNF ALPHA ACTIVITY OF THALIDOMIDE IN TNF ALPHA ARTHRITIS

说明(改编自申请)：药物沙利度胺为 20世纪60年代经常服用的晨间镇静剂S 疾病，但由于四致病原性而停止使用。然而， 这种药物对其非镇静剂的兴趣重新抬头。 和非胚胎效应，即其免疫调节活性。 沙利度胺是一种抗肿瘤坏死因子α制剂，已被 被描述为对治疗自身免疫性疾病有效 如麻风病，治疗因注射艾滋病毒而引起的疾病，如 口腔溃疡和恶病质与HIV-1的抑制 复制和艾滋病的进展。几位研究人员描述了 这一潜在重要的免疫调节作用相互矛盾 治疗方法仍不清楚。因此，拟议研究的重点是 目的是确定沙利度胺对正常C57BL/6小鼠和小鼠的影响。 人肿瘤坏死因子-α转基因C57BL/6小鼠。这些提出的假说 系列实验表明，沙利度胺的抗肿瘤坏死因子α活性 介导免疫调节作用，并将改变 细胞水平的免疫系统。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 可显著缓解易患关节炎的人肿瘤坏死因子- Alpha转基因小鼠；(3)确定沙利度胺是否改变 正常和转基因T细胞和β细胞的免疫活性 (4)沙利度胺对小鼠白细胞的影响 相互作用和程序性细胞死亡和凋亡。生成的数据 将提供有关行动的重要信息 细胞水平的沙利度胺。此外，这些实验 将允许在动物身上观察这种药物的活性 模型为人类最常见的自身免疫性疾病之一，关节炎。 最后，阐明了抗肿瘤坏死因子-α的作用机制 药物制剂可应用于其他自身免疫疾病的治疗 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.