CYTOKINE REGULATION OF PATHOLOGY IN SCHISTOSOMIASIS

血吸虫病病理学的细胞因子调节

• 批准号: 2071915
• 负责人: ADEL A. MAHMOUD
• 金额: $ 21.59万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-09-01 至 1998-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2071915
• 关键词: Schistosoma mansoni; baboons; biopsy; chemotherapy; cytokine; enzyme linked immunosorbent assay; genetic regulation; immunomodulators; interleukin 2; interleukin 4; liver; microorganism immunology; recombinant DNA; schistosomiasis; spleen; statistics /biometry; tumor necrosis factor alpha; urinary bladder

Our long-term goal is to understand the immunologic mechanisms that account for the egg-induced pathology and its modulation with chronic schistosomiasis. Intense study of the granulomatous responses in murine models and has produced a complicated picture of a dynamic T cell- dependent reaction in which cytokines coordinate the influx of effector cells to the granuloma. IL-2, IL-4, IL-10, and TNFalpha appear to play key roles in the induction and regulation of the granuloma. Whether these observations pertain to human disease is unknown. Because controlled and invasive studies in humans would be impossible, extension of these observations to a non human primates model that closely resemble human disease is of particular value. The present study proposes a series of experiments to determine the role and sequential expression of T cell derived cytokines have in the induction and modulation of egg-induced pathology in the baboon. Individual animals will undergo multiple serial biopsies of the spleen, liver, and bladder during the inductive, maintenance and modulatory phases of the granulomatous inflammation. These studies will correlate Th1 vs Th2 responses generated in the peripheral blood and spleen with the pattern of local cytokine responses produced in egg-induced granulomas. Additional animals will subsequently be administered recombinant human IL-12 or IL-4 at different periods during the acute infection to examine the role these cytokines have in altering the pattern of granuloma formation. Finally, the effects of curative chemotherapy on the subsequent granulomatous responses with re-infection will be examined. Because comparatively little is known about immune regulation of the granuloma in S, haematobium infections, studies will examine infection with this parasite as well as S. mansoni.

我们的长期目标是了解 胃电诱发的病理及其对慢性阻塞性肺疾病的调控 血吸虫病。对小鼠肉芽肿反应的深入研究 并制作了一张复杂的动态T细胞图片-- 细胞因子协调效应器内流的依赖反应 细胞转移到肉芽肿。IL-2、IL-4、IL-10和肿瘤坏死因子α似乎在其中发挥作用 在肉芽肿的诱导和调节中起关键作用。是否 这些关于人类疾病的观察是未知的。因为 在人体上进行受控和侵入性研究是不可能的，扩大 对一个非人类灵长类动物模型的观察 类似于人类的疾病具有特殊的价值。 目前的研究提出了一系列实验来确定这一角色 T细胞衍生细胞因子的顺序表达在 诱发和调节由卵子引起的狒狒的病理。 单个动物将接受多次连续的脾活检， 肝、膀胱的诱导、维持和调节 肉芽肿性炎症的分期。这些研究将相互关联 Th1与Th2在外周血和脾中产生的反应 卵子诱导的局部细胞因子反应模式 肉芽肿。随后将给更多的动物注射。 重组人IL-12或IL-4在急性期不同时期的变化 感染来检查这些细胞因子在改变 肉芽肿形成的模式。最后，治本的效果 化疗对继发性肉芽肿反应及再感染的影响 将会被检查。因为人们对免疫的了解相对较少 S对肉芽肿、血吸虫感染的调控研究将 检查这种寄生虫和曼氏葡萄球菌的感染情况。