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PROPHYLAXIS OF L. TROPICA INFECTIONS WITH CYCLOSPORINES

用环孢菌素预防热带乳杆菌感染

基本信息

批准号：
3436589
负责人：
NANCY C BEHFOROUZ
金额：
$ 6.43万
依托单位：
BALL STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1985
资助国家：
美国
起止时间：
1985-09-30 至 1988-01-31
项目状态：
已结题

项目摘要

The proposed study on the prophylaxis of Leishmania tropica infections in Balb/c mice with the known immunosuppressant Cyclosporine A and its analogue, B-5-49, will attempt to elucidate the drug-induced alteration in the host response to the parasite which enables this highly susceptible mouse strain to mount an effective curative immune response to the infecting protozoa. Leishmania tropica infections in Balb/c mice have been used as experimental models of both diffuse cutaneous and the frequently fatal systemic leishmaniasis in man. Our understanding, treatment and prevention of these two world-wide infections is strikingly incomplete or inadequate. It is hoped that this study will help to clarify the important immunomodulatory effects of the two cyclosporines which apparently prevents leishmania specific immunosuppression from developing during the infectious process. After determining the optimum protective treatment regimen for both drugs, the antigen-specific and non-specific immune responsiveness of infected, treated animals will be monitored and compared to non-treated controls. Specifically, the development and level of: 1) delayed type hypersensitivity, 2) anti-leishmanial antibodies and 3) resistance to parasite challenge will be determined over time as well as level of immune responsiveness in vitro in response to unrelated antigens (SRBC) and mitogens. Of particular interest will be the ability of lymphocytes from the experimental animals to produce lymphokines which are capable of stimulating macrophage cidal activity toward intracellular leishmania. The level of immunosuppression in treated, non-infected animals will also be determined to clearly establish the level of immunocompetence following the chosen treatment regimen for both drugs.

关于预防热带利什曼原虫感染的建议研究 BALB/c小鼠应用已知免疫抑制剂环孢素A及其受体类似物B-5-49将试图阐明药物引起的宿主对寄生虫的反应使这种高度敏感小鼠品系对该病毒产生有效的疗效免疫反应感染原生动物。Balb/c小鼠中的热带利什曼原虫感染已被既可作为弥漫性皮肤损伤的实验模型，也可作为常见的人类致命性系统性利什曼病。我们的理解、对待和对这两种世界性感染的预防是惊人的不完整或不够充分。希望这项研究将有助于澄清两种环孢菌素的免疫调节作用利什曼原虫感染期间发生的特异性免疫抑制进程。在确定最佳保护性治疗方案后这两种药物的抗原特异性和非特异性免疫反应性受感染的、经过治疗的动物将被监测，并与未治疗的动物进行比较。控制。具体地说，发展和水平：1)延迟型过敏，2)抗利什曼抗体和3)对寄生虫的挑战将随着时间和免疫水平的变化而确定对无关抗原的体外反应性(SRBC)和有丝分裂原。特别令人感兴趣的将是淋巴细胞从实验动物产生的淋巴因子能够刺激巨噬细胞对细胞内利什曼病的杀伤活性。这个接受治疗的非感染动物的免疫抑制水平也将是决心在以下情况下明确确定免疫能力水平为两种药物选择了治疗方案。