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Colistin stimulates the activity of neutrophil elastase and Pseudomonas aeruginosa elastase

Child Health-Division of Clinical Sciences, Sheffield Children's Hospital Trust, Sheffield, UK

CORRESPONDENCE: G.S. Evans, Child Health-Division of Clinical Sciences, Sheffield Children's Hospital Trust, Western Bank, Sheffield, S10 2TH, UK. Fax: 44 1142755364. E-mail: g.s.evans@sheffield.ac.uk

Keywords: colistin, neutrophil elastase, proteolysis, Pseudomonas

Received: March 26, 2001
Accepted January 18, 2002

This study was partly funded by the Sheffield Hospital Children's Fund.

Nonantimicrobial effects of antibiotics may contribute to their activity in the treatment of infective airway disease. The aim of this study was to identify antibiotics used for the treatment of infection in cystic fibrosis that may alter the activity of human neutrophil elastase (HNE) and Pseudomonas aeruginosa elastase (PE).

The effect of antibiotics on the activity of purified HNE and PE, and HNE in sputum was assessed using colourimetric and fluorescent substrate assays by kinetic measurements, and by examining the interaction of HNE with inhibitors.

Ceftazidime, tobramycin, and gentamycin slightly inhibited purified HNE activity whereas erythromycin and colistin significantly stimulated purified HNE and PE (395 and 557%, respectively). However, only colistin increased HNE activity in sputum (+102%) and was therefore studied in more detail. This increase in activity was not due an interference with the specific inhibition of HNE by ₁-antitrypsin but colistin was found to reverse the inhibitory effects of small molecular weight molecules like heparin.

Colistin increases the activity of human neutrophil elastase and Pseudomonas aeruginosa elastase, two proteases that contribute to the pathogenesis of cystic fibrosis airway disease.

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