Inhaled tacrolimus modulates pulmonary fibrosis without promoting inflammation in bleomycin-injured mice

No effective treatment is currently available for idiopathic pulmonary fibrosis (IPF) patients. Tacrolimus (Tac) has gained attention as a possible treatment due to its potent anti-fibrotic properties. Unfortunately, Tac induces multiple side effects including inflammation and renal insufficiency. We hypothesized that direct daily delivery of nebulized Tac-nanoparticle aggregates into the lungs (Tac inh ) would not only prevent fibrosis but also limit systemic complications. C57Bl6/J mice were given Tac by I.P. injection (Tac IP ) or Tac inh 1 h or 6 days after bleomycin injury. Residual inflammation and fibrosis were assessed in the lungs 21 days after bleomycin injury. Bleomycin-injured mice receiving Tac inh compared with those receiving Tac IP had a higher survival (100 and 83.3 %, respectively, vs. 49 %). Inflammation and fibrosis were significantly reduced in mice receiving Tac inh compared to mice receiving Tac IP . Tac inh may provide an effective and safer treatment for IPF. This finding revives the interest in this drug to treat IPF patients.