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. ? ?
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