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Components of the increased circulating proteolytic activity in pediatric burn patients
A N Neely1, G D Warden, M Rieman
1Department of Physiology and Biophysics, University of Cincinnati College of Medicine, Ohio.
Insights
Pediatric burn patients show increased proteolytic activity (PA) linked to burn severity and infection risk. This elevation stems from reduced proteinase inhibitors, elevated neutrophil elastase, and activated proteolytic cascades.
Area of Science:
- Biochemistry
- Immunology
- Pediatric Medicine
Background:
- Elevated total proteolytic activity (PA) is observed in pediatric burn patients.
- Increased PA correlates with burn severity (percent total body surface area burned) and susceptibility to infection.
Purpose of the Study:
- To investigate the sources of increased circulating PA in pediatric burn patients.
- To evaluate levels of proteinase inhibitors, proteinases, and proteolytic cascade activation.
Main Methods:
- Functional levels of antithrombin, alpha 2-antiplasmin, alpha 1-proteinase inhibitor, neutrophil elastase, plasminogen, and prekallikrein were measured.
- Assays were performed on 25 healthy children and 25 pediatric burn patients within the first week postburn.
Main Results:
- Levels of antithrombin, alpha 2-antiplasmin, plasminogen, and prekallikrein were significantly decreased postburn.
- Neutrophil elastase levels were significantly increased postburn.
- These changes indicate reduced proteinase inhibition and activation of proteolytic cascades.
Conclusions:
- Decreased proteinase inhibitors contribute to elevated PA in pediatric burn patients.
- Increased neutrophil elastase levels also contribute to elevated PA.
- Activation of circulating proteolytic cascade systems plays a role in increased total PA postburn.
Abstract:
Total proteolytic activity (PA) is increased in the circulation of pediatric burn patients. The extent of the increase correlates with the percent total body surface area (TBSA) burned and is associated with increased susceptibility to fatal infection. To determine the source or sources of this PA, three factors were evaluated: (1) levels of proteinase inhibitors--antithrombin, alpha 2-antiplasmin, and alpha 1-proteinase inhibitor; (2) levels of proteinase--neutrophil elastase; and (3) activation of circulating proteolytic cascade systems as indicated by changes in levels of system components--plasminogen and prekallikrein. All assays measured functional levels of the proteins. Normal levels were determined in 25 consecutive well children who were seeing their pediatrician for checkups (14 boys, 11 girls, ranging in age from 10 months to 17 years). Twenty-five consecutive burn victims admitted to the Shriners Burns Institute, Cincinnati Unit (19 boys, six girls, aged 10 months to 17 years), with a mean full-thickness burn of 43.2% TBSA (range, 6%-87%) were studied in the first week postburn. Antithrombin, alpha 2-antiplasmin, plasminogen, and prekallikrein levels decreased (p < 0.001) postburn, whereas elastase increased (p < 0.001). We conclude that, in pediatric burn patients, decreased proteinase inhibitors, increased proteinase, and activation of circulating proteinase cascades all contribute to elevated total circulating PA postburn.