A neutrophil elastase inhibitor, sivelestat, improves leukocyte deformability in patients with acute lung injury

• Published in: The journal of trauma Vol. 60; no. 5; p. 936
• Main Authors: Inoue, Yoshiaki, Tanaka, Hiroshi, Ogura, Hiroshi, Ukai, Isao, Fujita, Kieko, Hosotsubo, Hideo, Shimazu, Takeshi, Sugimoto, Hisashi
• Format: Journal Article
• Language: English
• Published: United States 01.05.2006
• Subjects: Adult; Aged; APACHE; C-Reactive Protein - metabolism; Cell Membrane - drug effects; Cell Membrane - physiology; Elasticity - drug effects; Female; Glycine - analogs & derivatives; Glycine - therapeutic use; Humans; Leukocyte Count; Leukocyte Elastase - antagonists & inhibitors; Leukocytes - drug effects; Leukocytes - physiology; Lung - blood supply; Lung Injury; Male; Microcirculation - drug effects; Middle Aged; Norepinephrine - blood; Oxygen - blood; Positive-Pressure Respiration; Respiratory Distress Syndrome, Adult - drug therapy; Respiratory Distress Syndrome, Adult - immunology; Rheology; Sulfonamides - therapeutic use; Systemic Inflammatory Response Syndrome - drug therapy; Systemic Inflammatory Response Syndrome - immunology; Total Lung Capacity - drug effects
• DOI: 10.1097/01.ta.0000217271.25809.a0
• ISSN: 0022-5282

The objective of this study was to evaluate whether the neutrophil elastase (NE) inhibitor, sivelestat, improves leukocyte deformability and pulmonary function in patients with acute lung injury (ALI). Twenty-four patients with systemic inflammatory response syndrome (SIRS) were divided into two groups: those with ALI (ALI group, n = 14), and those without ALI (non-ALI group, n = 10). Within 72 hours after the diagnosis, we measured the total leukocyte count (TLC), C-reactive protein (CRP) level, NE concentration, APACHE II score, Goris multiple organ failure (MOF) index, respiratory index (RI), lung injury score (LIS), and oxygenation index (P/F ratio). Leukocyte deformability was examined with a microchannel array etched on a single-crystal silicon tip that simulates the microvasculature. The number of obstructed microchannels (NOM) because of stiffened neutrophils and transit time (TT), defined as the time needed for 100 microL of whole blood to pass through the microchannels, were determined. We then administered sivelestat (4.8 mg/kg/d) to nine ALI patients (sivelestat group) for 5 days and compared with seven ALI patients treated previously without sivelestat (conventional group). The factors described above were measured before and 5 days after treatment. There were no significant differences in age, TLC, CRP, APACHE II score, and MOF index between ALI and non-ALI group. RI and LIS were higher and the P/F ratio was significantly lower in the ALI group than in the non-ALI group. NE concentration, NOM, and TT were significantly higher in the ALI group than in the non-ALI group (p < 0.05). After 5 days of treatment with sivelestat, the APACHE II score, MOF index, RI, LIS, NE concentration, TT, and NOM were lower and the P/F ratio was significantly higher than baseline values and those in the conventional group (p < 0.05). NE concentration and neutrophil rigidity are significantly increased in SIRS patients with ALI. Sivelestat appears to reduce NE concentration and neutrophil stiffness and improve pulmonary oxygenation in patients with ALI.