DEVELOP MODEL OF PNEUMOCYSTIS CARINII PNEUMONIA IN RHESUS MONKEY: SIV

恒河猴卡氏肺囊虫肺炎模型的开发：SIV

• 批准号: 6277446
• 负责人: JR RUDOLF P BOHM
• 金额: $ 8.66万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-30 至 1999-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6277446
• 关键词: AIDS; Mammalia; Primates; immunology; infection; inflammation; lymphatic system; model design /development; respiratory system; virus

Pneumocystis carinii pneumonia (PCP) is the most frequently reported opportunistic infectious complication in HIV infected individuals. Numerous rodent models of PCP are available. Occasionally PCP occurs in the simian immunodeficiency virus (SIV) infected rhesus monkey during the later immunosuppressive phase of disease. Unfortunately, the occurance of PCP is not predictable in SIV infected animals due to individual host variablility, different SIV strains used, and because of differences in prevalence of P. carinii in the environment. A reproducible model of PCP in rhesus monkeys could be utilized to study the pathogenesis of the disease and to allow drug therapy trials. Using previously published information on the PCP mouse model, we undertook a pilot study using dexamethasone to immunosuppress two rhesus monkeys. The animals were housed conventionally in a room in single cages. We followed the animals clinically by daily observation, weekly physical examination, weekly complete blood counts (CBC) and weekly serum chemistries. Dosing was instituted at 2.5 mg/kg IM every 12 hours. The dose was tapered over an eight week period to 0.5 mg/kg/day. Prophylactic antibiotic therapy was administered during treatment. Absolute lymphopenia occurred in both animals within the first week of dosing. Lymphocyt counts returned to normal by 35 days of treatment. This time point corresponded with the tapered dosing of 0.5 mg/kg/day. At no time during dosing was neutropenia noted. Physical examination revealed weight loss in both animals. One animal demondstrated failure to epithelialize a deep self-trauma bite wound that occurred during the initial days of the study. This wound later became infected and required discontinuation of dexamethasone and intensive multiple drug antibiotic therapy to cure. Future experiments will utilize conbination immunosuppressive drug protocols to minimize complications associated with high dose corticosteriod administration. The use of laminar flow housing will also be explored as well as the use of a broader spectrum

卡氏肺孢子虫肺炎（PCP）是最常见的 HIV感染者的机会性感染并发症 个体 有许多啮齿动物的五氯苯酚模型。 猿猴免疫缺陷病毒（SIV）偶尔会出现PCP 感染恒河猴在后期免疫抑制阶段 疾病 不幸的是，PCP的发生是不可预测的， SIV感染动物由于个体宿主的变异性， SIV菌株，并由于P。 环境中的卡氏虫 恒河猴PCP模型的建立 猴子可以用来研究疾病的发病机制， 允许药物治疗试验。 使用以前发布的信息 在PCP小鼠模型上，我们进行了一项使用地塞米松的初步研究， 免疫抑制两只恒河猴。 将动物圈养 传统上在一个房间里的单个笼子里。 我们跟着动物 通过每日观察、每周体格检查、每周 全血细胞计数（CBC）和每周血清化学检查。 给药 以2.5 mg/kg IM每12小时给药一次。 剂量逐渐减少， 为期8周，剂量为0.5 mg/kg/天。 预防性抗生素 在治疗期间给予治疗。 绝对淋巴细胞减少症 在给药的第一周内，两只动物均发生。 淋巴细胞 治疗35天后计数恢复正常。 该时间点 对应于0.5 mg/kg/天的逐渐减量给药。 任何时间概无 给药期间观察到中性粒细胞减少症。 理学检查发现 两只动物的体重减轻。 有一只动物证明， 使一个发生在 研究的最初几天。 这个伤口后来感染了， 需要停用地塞米松和强化多种药物 抗生素治疗治愈。 未来的实验将利用 联合免疫抑制药物方案，以尽量减少并发症 与高剂量皮质类固醇给药相关。 使用 层流住房也将探讨以及使用一个 更广谱