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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.

拟开展的预防热带利什曼原虫感染的研究用已知的免疫抑制剂环孢菌素A及其类似物，B-5-49，将试图阐明药物诱导的改变，宿主对寄生虫的反应使这种高度易感的小鼠品系，以建立有效的治疗性免疫反应，感染原生动物 Balb/c小鼠中的热带利什曼原虫感染已经被证实是用作弥漫性皮肤和经常致命的系统性利什曼病的人。我们的理解，治疗和对这两种全球性感染的预防是惊人的不完全，不足希望这项研究将有助于澄清重要的两种环孢菌素的免疫调节作用，利什曼原虫特异性免疫抑制在感染过程中的发展过程在确定了最佳的保护性治疗方案后，这两种药物，抗原特异性和非特异性免疫反应，将监测感染的治疗动物，并与未治疗动物进行比较对照具体而言，发展和水平：1）延迟型超敏反应，2）抗利什曼抗体和3）对寄生虫挑战将随着时间的推移以及免疫水平的确定，体外对无关抗原（SRBC）的反应性，有丝分裂原特别令人感兴趣的将是淋巴细胞的能力，实验动物产生淋巴因子，刺激巨噬细胞对细胞内利什曼原虫的杀灭活性。的治疗的未感染动物中的免疫抑制水平也将确定明确建立免疫活性水平后，选择两种药物的治疗方案。