Lactoferrin for Immunomodulation of Systemic Inflammatory Response Syndrome

描述(申请人提供)：该项目的总体目标是开发一种生物疗法来治疗全身炎症反应综合征(SIRS)，使用一种新型的人重组乳铁蛋白，该蛋白含有人源化的糖基化模式。SIRS是脓毒症和随后的组织损伤导致多器官衰竭之前复杂的急性期内在介质作用的临床表现。在脓毒症期间，免疫动态平衡丧失，导致破坏性的免疫病理。这项建议将研究乳铁蛋白在脂多糖(LPS)诱导的内毒素血症和活菌诱导的小鼠全身炎症发展过程中介导细胞反应的作用。与乳铁蛋白调节导致炎症和氧化应激的单核细胞反应相关的分子事件将被调查。该项目的总体假设是乳铁蛋白通过改变免疫介质和氧化应激源的相对数量来防止侮辱诱导的炎症反应进展为感染性休克，这些免疫介质和氧化应激对肠道结构和功能产生不利影响。

DESCRIPTION (provided by applicant): The overall goal of this project is to develop a biologic therapeutic to treat systemic inflammatory response syndrome (SIRS) using a novel human recombinant lactoferrin that contains "humanized" glycosylation patterns. SIRS is a clinical expression of the action of complex acute-phase intrinsic mediators that precedes sepsis and subsequent tissue damage leading to Multiple Organ Failure. During sepsis, immune homeostasis is lost leading to destructive immunopathology. This proposal will examine lactoferrin's effects to mediate cellular responses during the development of Lipopolysaccharide (LPS)-induced endotoxemia and live bacteria induced systemic inflammation in mice. The molecular events associated with lactoferrin mediation of monocytic responses that lead to inflammation and oxidative stress will be investigated. The overall hypothesis on this project is that lactoferrin protects against the progression of insult-induced inflammatory responses into septic shock by altering relative amounts of immune mediators and oxidative stressors which exert detrimental effects on gut structure and function.