Lactoferrin for Immunomodulation of Systemic Inflammatory Response Syndrome

乳铁蛋白用于全身炎症反应综合征的免疫调节

基本信息

批准号：
7217214
负责人：
JEFFREY K ACTOR
金额：
$ 20.37万
依托单位：
PHARMAREVIEW CORPORATION
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-05-01 至 2008-10-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7217214
关键词：
4 hydroxynonenal Acute Animal Model Antioxidants Apoptotic Bacteremia Bacteria Bacterial Translocation Biological Response Modifiers Bos taurus Cattle Cell Line Cells Clinical Clinical Protocols Complex Development Endotoxemia Endotoxins Enterobacteriaceae Escherichia coli Event Failure Goals Histology Homeostasis Human Hydrogen Peroxide Immune In Vitro Inflammation Inflammatory Inflammatory Response Interleukin-6 Intestines Lactoferrin Lead Life Lipopolysaccharides Measures Mediating Mediation Mediator of activation protein Milk Modeling Molecular Monitor Multiple Organ Failure Mus Nitric Oxide Oxidative Stress Pattern Phase Physiological Primary Cell Cultures Property Proteins Reactive Oxygen Species Recombinants Relative (related person)Sepsis Sepsis Syndrome Septic Shock Serum Source Stress Structure Symptoms TNF gene Therapeutic Time Tissues Treatment Protocols adduct base biological adaptation to stress body system chemokine cytokine glycosylation immunopathology immunoregulation in vivo novel protective effect research study response response to injury stressor

项目摘要

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.

描述（由申请人提供）：该项目的总体目标是开发一种生物治疗性，以使用一种新型的人类重组乳铁蛋白来治疗系统性炎症反应综合征（SIRS），该乳铁蛋白包含“人性化”糖基化模式。 SIRS是复杂的急性相位固有介体在败血症和随后导致多器官衰竭的组织损伤之前的作用的临床表达。在败血症期间，免疫稳态失去了导致破坏性免疫病理学。该提案将检查乳铁蛋白在脂多糖（LPS）诱导的内毒素血症的发展过程中介导细胞反应的作用，而活细菌引起了小鼠的全身性炎症。将研究与单核细胞反应的乳铁蛋白介导的分子事件，从而导致炎症和氧化应激。该项目的总体假设是，乳铁蛋白可以通过改变免疫介质的相对量和氧化应激源来防止侮辱性诱导的炎症反应向败血性休克的发展，从而对肠结构和功能产生有害的影响。