Lung inflammation is an early response to injury and may progress to fibrosis if unresolved. A bleomycin (BLM)-induced pulmonary injury mouse model was used to investigate inflammation-linked pathogenesis and to evaluate therapeutic interventions. Pirfenidone (PFD), an antifibrotic drug that inhibits fibroblast proliferation, was served as a positive control. In addition, two candidate compounds (C1 and C2) were evaluated for their potential to reduce early lung inflammation and lung barrier damage. Mice induced by inhaling BLM were treated with the compounds given intraperitoneally on days 1, 3 and 5. Bronchoalveolar lavage fluid (BALF) and serum were collected on day 10. Lung injury and inflammation were assessed by measuring total proteins and cytokine levels in the serum and BALF, including interleukin-6 (IL-6), interleukin-10 (IL-10), interleukin-1 beta (IL-1β), and tumor necrosis factor alpha (TNF-α). BLM induced severe lung injury and inflammation. PFD, C1 and C2 reduced BALF total cell counts by approximately 47%, 54% and 58% respectively, compared with BLM group, whereas BALF protein were unchanged. C1 reduced IL-6 in BALF by approximately 44%. Both PFD and C2 significantly reduced wet lung/body weight by approximately 17% and 21% respectively, and decreased serum IL-6 by approximately 46% (PFD) and 51% (C2). Overall, the interventions reduced BLM-induced inflammatory cell influx and C2 showing the most consistent effects. All treatments had limited effects on lung swelling and lung barrier damage at the measured time point. These data show that C2 should be a priority candidate for further investigation to define its mechanism, optimal dosing, and long-term outcomes.
Tianhao Fang (Thu,) studied this question.