Background and purpose:  The effects of a phosphodiesterase 4 (PDE4) inhibitor, roflumilast, on bleomycin‐induced lung injury were explored in ‘preventive’ and ‘therapeutic’ protocols and compared with glucocorticoids.

Experimental approach:  Roflumilast (1 and 5 mg·kg⁻¹·d⁻¹, p.o.) or dexamethasone (2.5 mg·kg⁻¹·d⁻¹, p.o.) was given to C57Bl/6J mice from day 1 to 14 (preventive) or day 7 to 21 (therapeutic) after intratracheal bleomycin (3.75 U·kg⁻¹). In Wistar rats, roflumilast (1 mg·kg⁻¹·d⁻¹, p.o.) was compared with methylprednisolone (10 mg·kg⁻¹·d⁻¹, p.o.) from day 1 to 21 (preventive) or from day 10 to 21 (therapeutic), following intratracheal instillation of bleomycin (7.5 U·kg⁻¹). Analyses were performed at the end of the treatment periods.

Key results:  Preventive. Roflumilast reduced bleomycin‐induced lung hydroxyproline, lung fibrosis and right ventricular hypertrophy; muscularization of intraacinar pulmonary vessels was also attenuated. The PDE4 inhibitor diminished bleomycin‐induced transcripts for tumour necrosis factor (TNFα), transforming growth factor (TGFβ), connective tissue growth factor, αI(I)collagen, endothelin‐1 and the mucin, Muc5ac, in lung, and reduced bronchoalveolar lavage fluid levels of TNFα, interleukin‐13, TGFβ, Muc5ac, lipid hydroperoxides and inflammatory cell counts. Therapeutic. In mice, roflumilast but not dexamethasone reduced bleomycin‐induced lung αI(I)collagen transcripts, fibrosis and right ventricular hypertrophy. Similar results were found in the rat.

Conclusions and implications:  Roflumilast prevented the development of bleomycin‐induced lung injury, and alleviated the lung fibrotic and vascular remodeling response to bleomycin in a therapeutic protocol, the latter being resistant to glucocorticoids.

Mandarin translation of abstract