CYTOKINE REGULATION OF PATHOLOGY IN SCHISTOSOMIASIS

我们的长期目标是了解免疫机制， 解释了卵诱导的病理学及其与慢性 血吸虫病 小鼠肉芽肿反应的深入研究 并绘制出了一幅复杂的动态T细胞图像 细胞因子协调效应物流入的依赖性反应 肉芽肿细胞。 IL-2、IL-4、IL-10和TNF α似乎在 在肉芽肿的诱导和调节中起关键作用。 是否 这些观察结果与人类疾病有关是未知的。 因为 控制和侵入性研究在人类将是不可能的，扩展 将这些观察结果与非人类灵长类动物模型进行比较， 类似人类疾病的研究具有特殊价值。 本研究提出了一系列的实验，以确定的作用 和T细胞衍生的细胞因子的顺序表达， 狒狒卵诱导病理的诱导和调节。 个体动物将经历脾脏的多次连续活检， 肝脏和膀胱在诱导，维持和调节 肉芽肿性炎症的阶段。 这些研究将与 Th 1与Th 2反应在外周血和脾脏中产生， 在鸡胚诱导的卵巢癌中产生的局部细胞因子反应模式 肉芽肿 随后将给予其他动物 重组人IL-12或IL-4在急性期不同时期的表达 感染，以检查这些细胞因子在改变 肉芽肿形成模式。 最后，疗效 化疗对随后的肉芽肿反应与再感染 将被审查。 因为相对而言， 调节血吸虫感染中的肉芽肿，研究将 检查这种寄生虫以及S. mansoni

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.