Lactoferrin for Immunomodulation of Systemic Inflammatory Response Syndrome

描述（由申请人提供）：本项目的总体目标是开发一种生物治疗剂，使用含有“人源化”糖基化模式的新型人重组乳铁蛋白治疗全身炎症反应综合征（SIRS）。SIRS是脓毒症和随后导致多器官衰竭的组织损伤之前的复杂急性期内在介质作用的临床表现。在脓毒症期间，免疫稳态丧失，导致破坏性免疫病理学。本研究将探讨乳铁蛋白在小鼠内毒素血症和活菌引起的全身性炎症中介导细胞反应的作用。与导致炎症和氧化应激的单核细胞反应的乳铁蛋白介导相关的分子事件将被研究。该项目的总体假设是，乳铁蛋白通过改变对肠道结构和功能产生有害影响的免疫介质和氧化应激源的相对量来防止由胰岛素诱导的炎症反应进展为脓毒性休克。

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.