Abstract
Background: A clinical study to investigate the leukotriene B4 (LTB4)-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.
| Original language | English |
|---|---|
| Pages (from-to) | 156-163 |
| Number of pages | 8 |
| Journal | Journal of Cystic Fibrosis |
| Volume | 13 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Mar 2014 |
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Keywords
- Anti-inflammatory treatment
- Cystic fibrosis
- Pulmonary infection
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine
- Pediatrics, Perinatology, and Child Health
- Medicine(all)
Cite this
BIIL 284 reduces neutrophil numbers but increases P. aeruginosa bacteremia and inflammation in mouse lungs. / Döring, Gerd; Bragonzi, Alessandra; Paroni, Moira; Aktürk, Firdevs Fatma; Cigana, Cristina; Schmidt, Annika; Gilpin, Deirdre; Heyder, Susanne; Born, Torsten; Smaczny, Christina; Kohlhäufl, Martin; Wagner, Thomas O F; Loebinger, Michael R.; Bilton, Diana; Tunney, Michael M.; Elborn, J. Stuart; Pier, Gerald B.; Konstan, Michael W.; Ulrich, Martina.
In: Journal of Cystic Fibrosis, Vol. 13, No. 2, 03.2014, p. 156-163.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - BIIL 284 reduces neutrophil numbers but increases P. aeruginosa bacteremia and inflammation in mouse lungs
AU - Döring, Gerd
AU - Bragonzi, Alessandra
AU - Paroni, Moira
AU - Aktürk, Firdevs Fatma
AU - Cigana, Cristina
AU - Schmidt, Annika
AU - Gilpin, Deirdre
AU - Heyder, Susanne
AU - Born, Torsten
AU - Smaczny, Christina
AU - Kohlhäufl, Martin
AU - Wagner, Thomas O F
AU - Loebinger, Michael R.
AU - Bilton, Diana
AU - Tunney, Michael M.
AU - Elborn, J. Stuart
AU - Pier, Gerald B.
AU - Konstan, Michael W.
AU - Ulrich, Martina
PY - 2014/3
Y1 - 2014/3
N2 - Background: A clinical study to investigate the leukotriene B4 (LTB4)-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.
AB - Background: A clinical study to investigate the leukotriene B4 (LTB4)-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.
KW - Anti-inflammatory treatment
KW - Cystic fibrosis
KW - Pulmonary infection
UR - http://www.scopus.com/inward/record.url?scp=84895067804&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84895067804&partnerID=8YFLogxK
U2 - 10.1016/j.jcf.2013.10.007
DO - 10.1016/j.jcf.2013.10.007
M3 - Article
C2 - 24183915
AN - SCOPUS:84895067804
VL - 13
SP - 156
EP - 163
JO - Journal of Cystic Fibrosis
JF - Journal of Cystic Fibrosis
SN - 1569-1993
IS - 2
ER -