Activity of neutrophil elastase reflects the progression of acute pancreatitis

Abstract

Objective. Neutrophil elastase (NE) concentration is associated with progression of acute pancreatitis (AP), but measuring total NE concentration includes biologically inactive NE. This study aims to investigate the relationship between NE activity and the aetiology and severity of AP and associated organ failure. Methods. Seventy-five patients admitted to our surgery department with a first episode of AP during 2004–2005 were age- and sex-matched to 20 healthy volunteers (controls). NE activity was assessed using venous blood samples obtained on patient admission and after 1, 2 and 14 days. One sample was also taken from each control. ANOVA was used for statistical comparison between groups. Results. Baseline NE activity (geometric mean; 95% confidence intervals) differed between patients (58.6 nM of substrate 7-amino-4-methylcoumarin [AMC]/hour; 48.52–70.72) and controls (31.5 nM AMC/hour; 25.5–39.0) (p = 0.0003), and did not correlate with time between symptom onset and admission. Patients with alcohol-induced AP demonstrated higher mean activity (59.1 nM AMC/h; 44.7–78.2) than those with gallstone-induced AP (41.7 nM AMC/h; 33.9–51.4) (p = 0.0496). NE activity was higher overall in patients with predicted severe AP (60.9 nM AMC/h; 48.0–77.2) than in those with predicted mild AP (42.1 nM AMC/h; 34.9–50.8) (p = 0.027). Patients with respiratory failure had higher NE activity (82.5 nM AMC/h; 57.5–118.4) than those without (43.9 nM AMC/h; 37.6–51.3) (p = 0.0024). Conclusions. NE activity was associated with predicted severity of AP and AP-associated respiratory failure. Specific NE inhibitors may have therapeutic potential in acute pancreatitis.

Key Words::

• Disease severity
• etiology
• leukocyte elastase
• multiple organ failure
• pancreatitis
• acute necrotizing

Acknowledgements

We thank Annika Sanfridson of AstraZeneca Research & Development, Lund for her invaluable contributions in planning and conducting the blood analyses. The authors are indebted to research laboratory nurse Ulla Hemmingsen and laboratory technician Elsa Justinussen for their assistance with blood samples and cytokine analysis.

Authors’ contributions

SN, AMA and MBH contributed to patient recruitment, and interpretation of data; MÅ performed the statistical analysis; TO and MN performed the measurements of neutrophil elastase; all authors contributed to conception and design of the study, and writing and revision of the manuscript.

Declaration of interest: MN, MA, TO and MBH are all employees of AstraZeneca. SN, AMA and LNJ report no conflicts of interest. The authors alone are responsible for the content and writing of the article.

This study was supported by grants from Snedkermester Sophus Jakobsen and wife Astrid Jacobsen's Foundation, the Augustinus Foundation, Else and Mogens Wedell-Wedellsborg's Foundation, and the Danish National Health Research Council (grant no: 271-05-0770). MN, MA, TO and MBH are all employees of AstraZeneca. We thank Dr Martin Bell, Dr Catriona Turnbull and Dr Michael Molloy-Bland of Oxford PharmaGenesis^™ Ltd for providing writing assistance funded by AstraZeneca R&D, Mölndal, Sweden.