PROTOCOL TO DEVELOP MODEL OF PNEUMOCYSTIS CARINII PNEUMONIA IN RHESUS MONKEY

恒河猴卡氏肺囊虫肺炎模型开发方案

• 批准号: 6116216
• 负责人: JR RUDOLF P BOHM
• 金额: $ 5.31万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-05-01 至 2000-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6116216
• 关键词: AIDS; Mammalia; communicable diseases; immunology; inflammation; lymphatic system; model design /development; respiratory system; virus

This study is a continuation of previously reported work to develop a rhesus monkey model of Pneumocystis carinii pneumonia (PCP). This model will be important to study the pathogenesis and novel drug compounds that may be used to treat PCP. Four rhesus monkeys were chosen for this pilot study. Three animals received alternate day dosing of prednisone and cyclophosphamide to induce immunosuppression. The fourth animal was used as a non-immunosuppressed control. Bronchoalveolar lavage (BAL) was performed one week prior to immunosuppression and weekly thereafter. All four animals were inoculated via a bronchoscope with a homogenate from P. carinii frozen lung tissue derived from three SIV infected animals. Viability was assessed prior to the time of inoculation. Five ml of homogenate (2.8 x 106 organisms/ml) was inoculated in the right caudal lung lobe of each animal. Followup included BAL, silver stain, PCR, bacterial culture, complete blood counts, serum chemistries, chest radiographs, and physical examinations performed at weekly intervals. Total lymphocyte counts in peripheral blood as well as CD4+ And CD8+ subsets decreased to a nadir by day 21. The lung homogenate was positive by DNA PCR for SIV at the time of inoculation. All four animals became positive by DNA PCR for SIV by 14 days post inoculation. BAL samples were negtive for P. carinii by PCR and by Giemsa stain evaluation at all time points. Silver stains of cytospin samples from BAL were also negative. Thoracic radiographs were normal throughout the study period. Future experiments will involve timing of inoculation at the nadir of the CD4+ lymphocyte count and inoculation of SIV-negative lung homogenate. FUNDING Base Grant PUBLICATIONS None

这项研究是以前报告的工作的延续， 建立恒河猴卡氏肺孢子虫肺炎（PCP）模型。 该模型的建立对研究该病的发病机制和新药开发具有重要意义 可用于治疗PCP的化合物。 四只恒河猴 选择了这个试点研究。 3只动物隔日接受 泼尼松和环磷酰胺的剂量以诱导免疫抑制。 第四只动物用作非免疫抑制对照。 治疗前一周进行支气管肺泡灌洗（BAL） 免疫抑制，此后每周一次。 四只动物都是 通过支气管镜接种冷冻卡氏肺孢子虫匀浆 来自三只SIV感染动物的肺组织。 活力 在接种前进行评估。 5 ml匀浆（2.8 x 106个微生物/ml）接种于 每一个动物。 随访包括BAL、银染、PCR、细菌学检查 培养，全血细胞计数，血清化学，胸部X光片， 每周进行一次体格检查。 总 外周血淋巴细胞计数以及CD 4+和CD 8+亚群 到第21天降至最低点。 肺组织匀浆呈阳性， 在接种时进行SIV的DNA PCR。 四只动物都变成了 接种后14天，SIV DNA PCR阳性。 BAL样品 通过PCR和Giemsa染色评价， 所有时间点。 来自BAL的细胞离心涂片样品的银染也被 阴性 整个研究期间胸部X线片正常 期 未来的实验将涉及接种的时间， CD 4+淋巴细胞计数和SIV阴性接种的最低值 肺匀浆。 基金基础赠款