6.4. Roflumilast and lung fibrosis
Because of the potential effect of anti-inflammatory treatment to
mitigate airway fibrotic remodeling, roflumilast might have
anti-fibrotic role due to its well-known anti-inflammatory action
(Hatzelmann et al., 2010).
Roflumilast was found to have the ability to prevent the progressive
airways fibrosis, as a result of antagonizing fibroblasts activity,
which could be mediated by TGF-β1, an essential regulator of immune
responses related to fibrosis (Togo et al., 2009). Anti-fibrotic profile
of roflumilast could be also explained by its ability to reduce the
expression of upregulated NADPH oxidase 4 (NOX4) (Milara et al., 2015c),
which was indicated to be critical for pulmonary fibrotic remodeling
(Amara et al., 2010).
Within this regard, roflumilast could also normalize most of increased
metabolic changes like alterations in oxidative equilibrium, increased
collagen and protein synthesis; resulting in decline in the fibrotic
score. Simultaneously, reduced lung tissue pH has been proposed as a
risk factor for lung fibrosis development, which was also reported to be
corrected by roflumilast in bleomycin model of pulmonary fibrosis
(Milara et al., 2015a).