Pneumologie 2016; 70 - P27
DOI: 10.1055/s-0036-1584630

The effect of the antiinflammatory IL-1R antagonist anakinra in mice with CF-like lung disease and Pseudomonas aeruginosa infection

A Schütte 1, Z Zhou-Suckow 1, J Schatterny 1, S Schmidt 1, S Hassel 1, M Weitnauer 1, A Dalpke 1, M Mall 1
  • 1University Hospital Heidelberg, TLRC Heidelberg

Introduction: Spontaneous neutrophilic inflammation can be triggered by hypoxic epithelial necrosis in mucus-obstructed airways via the release of IL-1a in Scnn1b-Tg mice with CF-like lung disease, as recently reported. In this model, the inhibition of the IL-1R-MyD88 pathway with the IL1-R antagonist anakinra reduced airway neutrophilia and structural lung damage (Fritzsching B. et al., AJRCCM 2015). However, effects of anakinra on airway inflammation and antibacterial host defense in the context of a Pseudomonas infection remain unknown. Thus, the aim of this study was to evaluate the effects of anakinra on neutrophilic inflammation and Pseudomonas infection in vivo in wild-type and Scnn1b-Tg mice with CF-like lung disease.

Methods: Scnn1b-Tg and wild-type mice were treated with anakinra (5 mg/10 g bodyweight) or vehicle (NaCl) subcutaneously b.i.d. and subsequently challenged with the P. aeruginosa strain PAO1 (˜2.5 × 107 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 × 103 ± 1.5 × 103cfu/ml (untreated) vs. 5.6 × 103 ± 3.8 × 103 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.

Supported by an EC grant (7th Framework Program No. 603038 CFMatters).