Correlation between Mortality and the Levels of Inter-Alpha Inhibitors in the Plasma of Patients with Severe Sepsis

• Published in: The Journal of infectious diseases Vol. 188; no. 6; pp. 919 - 926
• Main Authors: Lim, Yow-Pin, Bendelja, Kresimir, Opal, Steven M., Siryaporn, Edward, Hixson, Douglas C., Palardy, John E.
• Format: Journal Article
• Language: English
• Published: Chicago, IL The University of Chicago Press 15-09-2003; University of Chicago Press; Oxford University Press
• Subjects: Alpha-Globulins - immunology; Alpha-Globulins - pharmacokinetics; Alpha-Globulins - therapeutic use; Antibodies, Monoclonal - immunology; antithrombin III; Antithrombins; APACHE; Bacterial diseases; Bacterial sepsis; Biological and medical sciences; Blood plasma; Coagulation; Disease Models, Animal; Dosage; Enzyme linked immunosorbent assay; Escherichia coli; Escherichia coli Infections - drug therapy; Escherichia coli Infections - mortality; Health care administration; Human bacterial diseases; Humans; Infectious diseases; inter-alpha inhibitor protein; Medical sciences; Membrane Glycoproteins - immunology; Mortality; Neutrophils; Pathogenesis and Host Response; protein C; protein S; Sepsis; Septic shock; Severity of Illness Index; Shock, Septic - drug therapy; Shock, Septic - mortality; Systemic Inflammatory Response Syndrome - drug therapy; Systemic Inflammatory Response Syndrome - mortality; Trypsin Inhibitor, Kunitz Soybean; Human; Prognosis; Serine endopeptidases; Enzyme; Mortality; Enzyme inhibitor; Bacteremia; Blood plasma; Infection; Sepsis syndrome; Peptidases; Bacteriosis; Hydrolases; ELISA assay
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/377642

Inter-alpha inhibitor protein (IαIp) is an endogenous serine protease inhibitor in human plasma. Circulating IαIp levels were lower in 51 patients with severe sepsis than in healthy volunteers. Mean levels were 688±295 mg/L in patients with severe sepsis who survived (n=32), 486±193 mg/L in patients with sepsis who died (n=19), and 872±234 mg/L in control subjects (n=25). IαIp levels were lower in patients with shock versus those without (540±246 [n=33] vs. 746±290 [n=18] mg/L; P=.0102). IαIp levels were inversely correlated with 28-day mortality rates and Acute Physiology and Chronic Health Evaluation II scores and directly correlated with antithrombin III, protein C, and protein S levels. The administration of IαIp (30 mg/kg body weight intravenously) increased the 50% lethal dose in mice by 100-fold after an intravenous challenge of Escherichia coli. Thus, human IαIp may be a useful predictive marker and potential therapeutic agent in sepsis