PROTEASE INHIBITORS AND LPS INDUCED FEVER

蛋白酶抑制剂和 LPS 引起的发烧

• 批准号: 2695509
• 负责人: MATTHEW J KLUGER
• 金额: $ 2万
• 依托单位: LOVELACE RESPIRATORY RESEARCH INSTITUTE
• 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 2000-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2695509
• 关键词: acute phase protein; alpha 1 antitrypsin; body temperature regulation; gene targeting; genetically modified animals; hyperthermia; interleukin 1; interleukin 6; laboratory mouse; laboratory rat; lipopolysaccharides; macroglobulins; neutralizing antibody; protease inhibitor

Studies in this proposal focus on the mechanism by which the acute-phase proteins a1-antitrypsin (AAT) and a2-macroglobulin (AMG) act as positive modulators of fever. Because these proteins are protease inhibitors, the investigators hypothesize that they act by increasing the concentrations of pyrogenic cytokines in the circulatory system and the hypothalamus. The proposed studies are to test two potential models. The specific aims are to: 1. Test the hypothesis that AAT acts as an endogenous pyrogen during LPS-induced fever; 2. Test the hypothesis that AMG acts as an endogenous pyrogen during LPS-induced fever; 3. Test the hypothesis that circulating AAT and AMG modulate fever via the regulation of cytokine clearance.

本提案的研究重点是急性期的机制