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BIIL 284 reduces neutrophil numbers but increases P. aeruginosa bacteremia and inflammation in mouse lungs.

ABSTRACT: A clinical study to investigate the leukotriene B(4) (LTB(4))-receptor antagonist BIIL 284 in cystic fibrosis (CF) patients was prematurely terminated due to a significantly increased risk of adverse pulmonary events. We aimed to establish the effect of BIIL284 in models of Pseudomonas aeruginosa lung infection, thereby contributing to a better understanding of what could have led to adverse pulmonary events in CF patients.P. aeruginosa DNA in the blood of CF patients during and after acute pulmonary exacerbations and in stable patients with non-CF bronchiectasis (NCFB) and healthy individuals was assessed by PCR. The effect of BIIL 284 treatment was tested in an agar bead murine model of P. aeruginosa lung infection. Bacterial count and inflammation were evaluated in lung and other organs.Most CF patients (98%) and all patients with NCFB and healthy individuals had negative P. aeruginosa DNA in their blood. Similarly, the P. aeruginosa-infected mice showed bacterial counts in the lung but not in the blood or spleen. BIIL 284 treatment decreased pulmonary neutrophils and increased P. aeruginosa numbers in mouse lungs leading to significantly higher bacteremia rates and lung inflammation compared to placebo treated animals.Decreased airway neutrophils induced lung proliferation and severe bacteremia in a murine model of P. aeruginosa lung infection. These data suggest that caution should be taken when administering anti-inflammatory compounds to patients with bacterial infections.

SUBMITTER: Doring G

PROVIDER: S-EPMC4163938 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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BIIL 284 reduces neutrophil numbers but increases P. aeruginosa bacteremia and inflammation in mouse lungs.

Döring Gerd G Bragonzi Alessandra A Paroni Moira M Aktürk Firdevs-Fatma FF Cigana Cristina C Schmidt Annika A Gilpin Deirdre D Heyder Susanne S Born Torsten T Smaczny Christina C Kohlhäufl Martin M Wagner Thomas O F TO Loebinger Michael R MR Bilton Diana D Tunney Michael M MM Elborn J Stuart JS Pier Gerald B GB Konstan Michael W MW Ulrich Martina M

Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society 20131031 2

<h4>Background</h4>A clinical study to investigate the leukotriene B(4) (LTB(4))-receptor antagonist BIIL 284 in cystic fibrosis (CF) patients was prematurely terminated due to a significantly increased risk of adverse pulmonary events. We aimed to establish the effect of BIIL284 in models of Pseudomonas aeruginosa lung infection, thereby contributing to a better understanding of what could have led to adverse pulmonary events in CF patients.<h4>Methods</h4>P. aeruginosa DNA in the blood of CF p ...[more]

PMID: 24183915

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Dataset Information

BIIL 284 reduces neutrophil numbers but increases P. aeruginosa bacteremia and inflammation in mouse lungs.

Publications

BIIL 284 reduces neutrophil numbers but increases P. aeruginosa bacteremia and inflammation in mouse lungs.

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