Inter-alpha Inhibitors in Neonatal Sepsis

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DESCRIPTION (provided by applicant): The primary goal of this research is to demonstrate the feasibility of Inter-alpha inhibitor proteins (Ialp) as potential therapeutic agents in neonatal sepsis. Ialp are natural serine protease inhibitors found in relatively high concentration in human adult and newborn plasma (ranges between 0.6-1.2 mg/mL). Ialp have been implicated in play roles in inflammation, wound healing and cancer metastasis. The high level of Ialp circulating normally in plasma indicates that the proteins are essential for life and no person with complete absence of Ialp has ever been detected. A significant decrease of plasma Ialp levels occurs in plasma of adult patients with severe sepsis and septic shock and the decrease correlates with the mortality. Our preliminary results suggest a similar decrease of Ialp levels in clinically proven neonatal sepsis suggesting the involvement of Ialp in the pathogenesis of neonatal sepsis. We hypothesize that administration of Ialp restore the imbalance between these natural protective inhibitors and destructive proteases will prevent organ injury and ultimately reduce the mortality in sepsis. Our animal studies using a polymicrobial sepsis rat model of cecal ligation and puncture (CLP) have already demonstrated the beneficial effects of Ialp in maintaining hemodynamic stability, preventing organ injury, and improving survival during the progression of sepsis in adult animals.