engleski

Inter-alpha Inhibitor Protein (IaIp) Administration Improves Survival in Sepsis in Neonatal Mice

Background: IaIp are group of serine proteases inhibitors found in a relatively high concentration in plasma. 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. Objective: The aim of this study is to evaluate the effects of parenterally administered IaIp in LPS induced sepsis in neonatal mice. Design/Methods: Sepsis was induced in 2 days old BALB/c mice with a subcutaneous injection of 25 micrograms of E. Coli derived LPS. An LPS dose response curve of lethality was determined. In 2 days old mice, 25 micrograms of LPS injected subcutaneously had a survival rate of 30% after 80 hours. In the subsequent experiment, two day old animals (n=22) were injected with this dose of LPS and then randomized into two groups. The treatment group (n=12) received an intraperitoneal injections of 60 micrograms of highly purified human IaIp one hour after the infection. The control group (n=10) received equal amount of human albumin. Results: Only 30% pups in the control group survived 80 hours after the infection of LPS in contrast to a 83% survival in the treatment group (Longrank test p value=0.0159). This data is representative of multiple experiments. Conclusions: These results suggest that administration of IaIp offers a beneficial effect in septic newborn mice and warrant further investigation.

eonatal sepsis; inter alpha inhibitor protein; LPS

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