INFECTIOUS ARTHRITIS AND CARTILAGE DESTRUCTION

感染性关节炎和软骨破坏

基本信息

批准号：
3155459
负责人：
DAVID J SCHURMAN
金额：
$ 18.44万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1988
资助国家：
美国
起止时间：
1988-07-01 至 1991-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3155459
关键词：
Staphylococcus infection antibacterial antibody antibiotics antibody titering antiinflammatory agents arthritis cartilage disorder combination chemotherapy corticosteroids immunotherapy interleukin 1 interleukin 2 laboratory rabbit medical complication nonhuman therapy evaluation secondary infection skeletal pharmacology

项目摘要

The long-term objectives of this proposal are to establish biochemical mechanisms underlying continued cartilage destruction in staphylococcal bacterial arthritis and to develop therapeutic regimens to prevent post-infectious inflammatory cartilage destruction. The rationale for the experiments is based on our results showing that staphylococcal joint infection results in rapid, direct effects on cartilage degradation and loss of proteoglycan and that cartilage destruction continues in spite of antibiotic treatment. The hypotheses to be tested are: (a) that antibiotic treatment coupled with treatment of the host-inflammatory reaction will decrease staph-induced cartilage degradation and (b) that inhibiting the post-infectious inflammatory reaction will prevent continued cartilage destruction and stimulate cartilage recovery. The Specific Aims are: (1a) Characterize long-term staph-induced cartilage degradation following antibiotic treatment at 24 and 48 hours post-infection at three, six and twelve months and (lb) determine short term (3 weeks post-infection) effects of adding supplemental anti-inflammatory treatment coincident with onset of antibiotic therapy; (2) Assess the recuperative capacity of articular cartilage in vitro following onset of cartilage degradation and in vivo following antibiotic and antiinflammatory therapy; (3) Isolate the staphylococcal proteoglycan releasing factor and characterize the molecular basis of staph factor induced cartilage degradation in vitro; (4) Prepare antibodies to the staph factor and apply the antibodies to the onset of staph induced cartilage destruction and test the antibody reactivities against interleukin 1. Experiments will be carried out in our established in vitro and in vivo models of staph infectious arthritis; effects of antibiotic and anti-inflammatory therapies will be assessed by quantitation of cartilage proteoglycan synthesis and degradation. Anti- inflammatory treatment will consist of administration of corticosteroids, nonsteroidal anti-inflammatory reagents and interleukin 2. Additional anti-inflammatory regimens will include aspiration with metal dependent enzyme inhibitors and non-ionic detergents. Purification of the staph factor will include FPLC ion-exchange chromatography.

该提案的长期目标是建立软骨持续破坏的生化机制葡萄球菌细菌性关节炎并开发治疗方法预防感染后炎症软骨的方案破坏。实验的基本原理是基于我们的结果表明，葡萄球菌关节感染导致对软骨退化和丧失产生快速、直接的影响蛋白多糖和软骨破坏仍在继续抗生素治疗。要检验的假设是： (a) 抗生素治疗与宿主炎症反应的治疗相结合减少葡萄球菌引起的软骨退化，并且 (b) 抑制感染后炎症反应可预防持续软骨破坏并刺激软骨恢复。具体目标是： (1a) 表征长期葡萄球菌诱导的 24 岁和 48 岁抗生素治疗后软骨退化感染后三、六个月和十二个月的小时数以及（磅）确定添加的短期（感染后 3 周）效果发病时补充抗炎治疗抗生素治疗； (2) 评估恢复能力软骨发生后的体外关节软骨抗生素和抗炎药后的降解和体内治疗; (3) 分离释放蛋白多糖的葡萄球菌因子并表征葡萄球菌因子诱导的分子基础体外软骨降解； (4) 制备葡萄球菌抗体因素并将抗体应用于葡萄球菌诱导的发病软骨破坏并测试抗体反应性白细胞介素1. 实验将在我们建立的体外和体内进行金黄色葡萄球菌感染性关节炎的体内模型；抗生素的影响抗炎治疗将通过定量评估软骨蛋白多糖的合成和降解。反对- 炎症治疗包括施用皮质类固醇、非类固醇抗炎剂和白细胞介素 2. 其他抗炎治疗方案包括使用金属依赖性酶抑制剂和非离子型药物进行抽吸洗涤剂。葡萄球菌因子的纯化将包括 FPLC 离子交换色谱法。