engleski

Beneficial Effects of Inter-alpha Inhibitor Proteins (IaIp) in an in vivo Animal Model of Neonatal Sepsis

Background: IaIp are group of serine proteases inhibitors. They are important in vivo modulators of endogenous proteases including trypsin, human leukocyte elastase, plasmin and cathepsin G. Release of endogenous proteases plays an important role in inflammation, sepsis, wound healing and metastasis. A significant decrease of plasma IaIp levels occurs in adult and newborn sepsis. Our previous animal studies using the polymicrobial sepsis rat (adult) model of cecal ligation and puncture demonstrated the beneficial effects of intravenous IaIp administration in improving morbidity and mortality. Objective: The aim of this study is to evaluate the effects of parenterally administered IaIp in an in vivo animal model of neonatal sepsis. Design/Methods: Sepsis was induced in 2-3 days old Fischer rats with a subcutaneous injection of E. Coli (BORT). A bacterial dose response curve of lethality was determined. 2 CFU/gram body weight was lethal at 40-50 hours after the infection. In the subsequent experiment, three day old animals (n=8) were injected with this dose of E. Coli and then randomized into two groups. The treatment group (n=4) received three intraperitoneal injections of 250 micrograms of purified human IaIp, at 6, 12 and 24 hours after the infection. The control group received equal amount of human albumin at the same time intervals. Results: All pups in the control group died within 40-44 hour after the infection. Animals in the treatment group survived up to 78 hours. Conclusions: These results suggest that IaIp offers a beneficial effect in septic newborn rats and warrant further investigation. Questions being pursued include: optimal dose vs. response to IaIp, optimal timing of IaIp administration, pharmacokinetics of IaIp, effectiveness of IaIp in other models of sepsis (E.g. Group B strep, LPS).

neonatal sepsis; Inter-alpha inhibitor protein; LPS

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