Correlation between mortality and the levels of inter-alpha inhibitors in the plasma of patients with severe sepsis.
Inter-alpha inhibitor protein (IalphaIp) is an endogenous serine protease inhibitor in human plasma. Circulating IalphaIp 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). IalphaIp levels were lower in patients with shock versus those without (540+/-246 [n=33] vs. 746+/-290 [n=18] mg/L; P=.0102). IalphaIp 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 IalphaIp (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 IalphaIp may be a useful predictive marker and potential therapeutic agent in sepsis.
Lim
Yow-Pin
YP
Brown Medical School, Division of Medical Oncology/Department of Medicine, Rhode Island Hospital, Providence, Rhode Island, USA. Yow-Pin_Lim_MD@Brown.edu
Bendelja
Kresimir
K
Opal
Steven M
SM
Siryaporn
Edward
E
Hixson
Douglas C
DC
Palardy
John E
JE
D018806:APACHE; D000510:Alpha-Globulins / Q000276:immunology / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000276:immunology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D004927:Escherichia coli Infections / Q000188:drug therapy / Q000401:mortality; D006801:Humans; D008562:Membrane Glycoproteins / Q000276:immunology; D012720:Severity of Illness Index; D012772:Shock, Septic / Q000188:drug therapy / Q000401:mortality*; D018746:Systemic Inflammatory Response Syndrome / Q000188:drug therapy / Q000401:mortality*; D014360:Trypsin Inhibitor, Kunitz Soybean
D000510:Alpha-Globulins; D000911:Antibodies, Monoclonal; D008562:Membrane Glycoproteins; C109148:SPINT2 protein, human; C011877:inter-alpha-inhibitor; D014360:Trypsin Inhibitor, Kunitz Soybean