The effect of the antiinflammatory IL-1R antagonist anakinra in mice with CF-like lung disease and Pseudomonas aeruginosa infection
A Schütte, Z Zhou-Suckow, J Schatterny… - …, 2016 - thieme-connect.com
A Schütte, Z Zhou-Suckow, J Schatterny, S Schmidt, S Hassel, M Weitnauer, A Dalpke…
Pneumologie, 2016•thieme-connect.comMethods: Scnn1b-Tg and wild-type mice were treated with anakinra (5 mg/10 g bodyweight)
or vehicle (NaCl) subcutaneously bid and subsequently challenged with the P. aeruginosa
strain PAO1 (2.5× 10 7 cfu/mouse) or vehicle (PBS) by intratracheal instillation.
Bronchoalveolar lavage (BAL) was performed 24h after Pseudomonas infection and
analyzed using differential cell counts, cytometric bead assay to measure proinflammatory
cytokines and quantitative microbiology. Results: A robust neutrophilic inflammation in both …
or vehicle (NaCl) subcutaneously bid and subsequently challenged with the P. aeruginosa
strain PAO1 (2.5× 10 7 cfu/mouse) or vehicle (PBS) by intratracheal instillation.
Bronchoalveolar lavage (BAL) was performed 24h after Pseudomonas infection and
analyzed using differential cell counts, cytometric bead assay to measure proinflammatory
cytokines and quantitative microbiology. Results: A robust neutrophilic inflammation in both …
Methods: Scnn1b-Tg and wild-type mice were treated with anakinra (5 mg/10 g bodyweight) or vehicle (NaCl) subcutaneously bid and subsequently challenged with the P. aeruginosa strain PAO1 (2.5× 10 7 cfu/mouse) or vehicle (PBS) by intratracheal instillation. Bronchoalveolar lavage (BAL) was performed 24h after Pseudomonas infection and analyzed using differential cell counts, cytometric bead assay to measure proinflammatory cytokines and quantitative microbiology.
Results: A robust neutrophilic inflammation in both wild-type and Scnn1b-Tg mice was induced by the acute infection with PAO1. However, treatment with anakinra reduced neutrophils in infected wild-type and Scnn1b-Tg mice (n= 13–15, P< 0.01). Despite this reduction, anakinra treatment did neither aggravate the acute PAO1 infection in wild-type nor in Scnn1b-Tg mice (1.9× 10 3±1.5× 10 3 cfu/ml (untreated) vs. 5.6× 10 3±3.8× 10 3 cfu/ml (treated), n= 13–14, P> 0.4).
Discussion: Our results support that treatment with the IL-1R antagonist anakinra reduces neutrophilic inflammation without exacerbating bacterial infection in CF-like lung disease in mice. Thus, anakinra may be used as a novel anti-inflammatory approach to control overwhelming neutrophilic airway inflammation without aggravating bacterial infection in CF. However, clinical studies are warranted to test the safety and efficacy of this anti-inflammatory strategy in patients with CF.
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