Proteolysis in severe sepsis is related to oxidation of plasma protein

Objective: To test the hypothesis that the oxidation of proteins is part of the mechanism of proteolysis in catabolic states. Design: Prospective, observational study. Setting: Critical care unit at a university teaching hospital, New Zealand. Patients: 13 patients (6 male, 7 female; median age 61, range 26-76 years) who were admitted to the Department of Critical Care Medicine at Auckland Hospital with a diagnosis of severe sepsis. The median APACHE II score during the first 24 hours after admission was 22 (range 15-34). Control values of protein carbonyl in plasma were established in 15 healthy volunteers. Interventions: We made serial measurements of total body protein (by neutron activation analysis) and plasma protein carbonyl (by ELISA) concentrations over a period of 10 days. Main outcome measure: Plasma protein carbonyl concentration and total body protein. Results: The total amount of body protein decreased significantly over the 10 days (p < 0.001). Plasma protein carbonyl concentrations were significantly higher in the septic patients than in the control group throughout the study period (p < 0.0001). There was a significant reduction in plasma protein carbonyl concentration over the study period (p < 0.008). The early increase in the concentration of protein carbonyl formation was followed by an ongoing loss of body protein. There was a significant positive correlation between total body protein and plasma protein carbonyl (p < 0.03). Conclusions: Severe sepsis results in oxidation of plasma proteins and this precedes and is related to the loss of body protein.