IMMUNOMODULATION OF RETROVIRAL CARDIOPATHOLOGY

描述 (摘自申请者摘要)心包积液、心肌病、 左心功能不全在艾滋病患者中很普遍。这个 申请者的小鼠逆转录病毒感染模型模仿了大部分免疫 在艾滋病毒感染期间发现的功能障碍和心脏毒性。他们期待着 细胞因子失调和小鼠氧化应激增加 心脏因小鼠感染逆转录病毒会增加NFkB的形成 导致ICAM-1和T辅助细胞过度激活的表达 细胞因子的分泌。这种级联反应将刺激中性粒细胞和内皮细胞 激活细胞并促进iNOS的形成，导致心脏 肌肉和内皮细胞损伤和心功能不全。他们会 对核内NFkB易位进行分子分析。他们会 同时测量iNOS或iNOS的结果RNA消息和蛋白质 ICAM-1在心脏组织中的表达。左心功能将被量化。 在活体内用压力-容量环来定义心功能不全 描述免疫调节剂的治疗效果。他们提议 研究中性粒细胞介导的心脏和冠状动脉组织损伤假说 血管紧张剂。他们将调查中性粒细胞的隔离和激活 心脏和氧化损伤测试。他们将把逆转录病毒 活体冠状动脉微血管损伤的研究进展 显微镜观察、中性粒细胞积聚和中性粒细胞功能。他们将限制 预防逆转录病毒感染对心脏的不良影响 功能失调的细胞因子的产生，减缓了由此产生的免疫 调节失调和氧化损伤增加。他们将审查 他们被证明的预防大部分细胞因子的方法的有效性 心脏的调节失调和氧化损伤：T细胞受体Vbeta8.1 注射、维生素E补充剂和干扰素-γ或抗IL-4 抗血清注射。它们还将通过以下方式加剧细胞因子失调 注射IL-4可加速免疫功能障碍和心脏病理改变。这些 模型研究将增加对逆转录病毒诱导免疫的理解 心脏功能障碍及其在心脏病理中的作用。这些治疗方法发现 预防逆转录病毒感染的细胞因子失调和心脏毒性 然后小鼠将适用于减少艾滋病病毒感染的心脏病 患者(摘要结束)

DESCRIPTION (Adapted from applicant's abstract) Pericardial effusion, cardiomyopathy, and left ventricular dysfunction are prevalent in patients with AIDS. The applicants' model of murine retrovirus infection mimics much of the immune dysfunction and cardiac toxicity found during HIV infection. They expect that cytokine dysregulation and increased oxidative stress in the mouse heart due to murine retrovirus infection will increase the formation of NfkB expression resulting in of ICAM-1 and T-helper cell hyperactivtion and secretion of cytokines. This cascade will stimulate PMN and endothelial cell activation and promote the formation of iNOS, resulting in cardiac muscle and endothelial cell damage and ventricular dysfunction. They will perform molecular analysis of NfkB translocation to the nucleus. They will measure simultaneously the resulting RNA message and proteins for iNOS or ICAM-1 in heart tissues. The left ventricular function will be quantitated in vivo with pressure volume loop to define the ventricular dysfunction and characterize the therapeutic effect of immunomodulators. They propose to examine the PMN-mediated tissue injury hypothesis in the heart and coronary vasculative. They will investigate PMN sequestration and activation in the heart and test for oxidative damage. They will correlate the retroviral progression to the coronary microvascular injury through intravital microscopy, PMN accumulation and PMN function. They will limit the deleterious cardiac effects during retrovial infection by preventing dysfunctional cytokine production, slowing the resulting immune dysregulation and increased oxidative damage. They will examine the efficacy of their proven methods that prevented much of the cytokine dysregulation and oxidative damage to the heart: T-cell receptor Vbeta 8.1 injection, vitamin E supplementation, and interferon-gamma or anti IL-4 antisera injection. They will also accentuate cytokine dysregulation by IL-4 injection to accelerate immune dysfunction and cardiopathology. These model studies will increase understanding of retrovirus induced immune dysfunction and its role in cardiac pathology. The treatments that found to prevent cytokine dysregulation and cardiotoxicitiy in retrovirally infected mice will then be applicable to reducing heart disease in HIV infected patients (End of Abstract)