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J Cyst Fibros. 2014 Mar;13(2):156-63. doi: 10.1016/j.jcf.2013.10.007. Epub 2013 Oct 31.

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

Author information

1
Institute of Medical Microbiology and Hygiene, Universitätsklinikum Tübingen, Tübingen, Germany.
2
Infection and Cystic Fibrosis Unit, Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute, Milano, Italy. Electronic address: bragonzi.alessandra@hsr.it.
3
Infection and Cystic Fibrosis Unit, Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute, Milano, Italy.
4
Queen's University Belfast, Northern Ireland, UK.
5
Klinik Schillerhöhe, Robert-Bosch Krankenhaus, Gerlingen, Germany.
6
Universitätsklinikum Frankfurt, Frankfurt, Germany.
7
Royal Brompton Hospital, London, UK.
8
Division of infectious Diseases, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
9
Case Western Reserve University, UH Rainbow Babies & Children's Hospital, Cleveland, OH, USA.

Abstract

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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.

KEYWORDS:

Anti-inflammatory treatment; Cystic fibrosis; Pulmonary infection

PMID:
24183915
PMCID:
PMC4163938
DOI:
10.1016/j.jcf.2013.10.007
[Indexed for MEDLINE]
Free PMC Article

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