Rapamycin Regulates Bleomycin-Induced Lung Damage in SP-C-Deficient Mice

Abstract EN

Injury to the distal respiratory epithelium has been implicated as an underlying cause of idiopathic lung diseases.

Mutations that result in SP-C deficiencies are linked to a small subset of spontaneous and familial cases of interstitial lung disease (ILD) and interstitial pulmonary fibrosis (IPF).

Gene-targeted mice that lack SP-C (Sftpc-/-) develop an irregular ILD-like disease with age and are a model of the human SP-C related disease.

In the current study, we investigated whether rapamycin could ameliorate bleomycin-induced fibrosis in the lungs of Sftpc-/- mice.

Sftpc+/+ and −/− mice were exposed to bleomycin with either preventative administration of rapamycin or therapeutic administration beginning eight days after the bleomycin injury.

Rapamycin-treatment increased weight loss and decreased survival of bleomycin-treated Sftpc+/+ and Sftpc-/- mice.

Rapamycin did not reduce the fibrotic disease in the prophylactic or rescue experiments of either genotype of mice.

Further, rapamycin treatment augmented airway resistance and reduced lung compliance of bleomycin-treated Sftpc-/- mice.

Rapamycin treatment was associated with an increased expression of profibrotic Th2 cytokines and reduced expression of INF-γ.

These findings indicate that novel therapeutics will be required to treat individuals with SP-C deficient ILD/IPF.