PROTOCOL TO DEVELOP MODEL OF PNEUMOCYSTIS CARINII PNEUMONIA IN RHESUS MONKEY

这项研究是先前报道的工作的继续 建立卡氏肺孢子虫肺炎(PCP)恒河猴模型。 该模型对研究其发病机制和新药开发具有重要意义。 可用于治疗五氯苯酚的化合物。四只恒河猴被 被选为这项初步研究的对象。三只动物隔天收到 强的松和环磷酰胺剂量诱导免疫抑制。 第四只动物被用作非免疫抑制对照。 治疗前一周行肺泡灌洗(BAL) 免疫抑制，此后每周一次。这四只动物都是 通过支气管镜接种冰冻卡氏肺孢子虫的匀浆 肺组织取自三只受SIV感染的动物。生存能力是 在接种前进行评估。5毫升匀浆(2.8 ×106菌/毫升)接种于小鼠右肺尾叶。 每只动物。随访包括BAL、银染、聚合酶链式反应、细菌培养 培养，全血细胞计数，血清化学，胸片， 每周进行一次体检。总计 外周血中淋巴细胞计数及CD4+和CD8+亚群 到第21天降到了最低点。肺组织匀浆呈阳性反应 接种时进行SIV的DNA聚合酶链式反应。所有四只动物都变成了 接种后14天DNA-PCR检测SIV阳性。BALL样本 经聚合酶链式反应和Giemsa染色检测均为阴性 所有的时间点。来自BAL的细胞旋体样本的银染也 不是。在整个研究过程中，胸片都是正常的。 句号。未来的实验将涉及到在 CD4+淋巴细胞计数的最低点与SIV阴性疫苗的接种 肺匀浆。资助基础赠款出版物无

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