Efficacy of dexamethasone, roflumilast and azithromycin in a murine cigarette smoke/NTHi infection model

Background: Smoking is a central risk factor for the development of Chronic Obstructive Pulmonary Disease (COPD) and Nontypeable Haemophilus Influenzae (NTHi) is expected to be an important trigger of exacerbations. Steroids, PDE-4 inhibitors and macrolides are used as treatment options. Aims and objectives: To investigate the effects of Dexamethasone, Roflumilast and Azithromycin in a murine cigarette smoke (CS)/NTHi infection model. Methods: Mice were exposed to CS and infected with NTHi. Animals were treated in a preventive manner with Dexamethasone, Roflumilast or Azithromycin each day of the experiment. Resistance and compliance were measured. Cell counts and bacterial load were determined in BAL fluid. Cytokines/chemokines were assessed in lung homogenate. Results: CS exposure and NTHi infection led to pulmonary neutrophil and macrophage accumulation. Pro-inflammatory cytokines/chemokines were elevated in lung homogenate. Dexamethasone, Roflumilast and Azithromycin treatment failed to reduce numbers of total cells and neutrophils. Moreover, dexamethasone treatment increased bacterial load and resulted in increased loss of body-weight. However, IFN-γ and IL-6 levels were reduced. Roflumilast had no pronounced effects on cytokines/chemokines but improved compliance. Treatment with azithromycin reduced bacterial load but had no effect on cytokines/chemokines or compliance. Conclusions: These results suggest that treatment with Dexamethasone, Roflumilast or Azithromycin might not be efficient to reduce CS and NTHi induced pulmonary inflammation. Treatment with Dexamethasone might increase the bacterial load, while Azithromycin could help to reduce the bacterial burden.