Thymosin β4 protects C57BL/6 mice from bleomycin‐induced damage in the lung

Abstract Background Thymosin β4 ( T β4) was recently found at high concentration in the bronchoalveolar lavage fluid ( BALF ) of scleroderma patients with lung involvement. It has been hypothesized that T β4 may exert a cyto‐protective effect during lung injury because lower T β4 levels were associated with interstitial lung disease progression. Moreover, T β4 treatment prevented profibrotic gene expression in cardiac cells in vitro and in vivo . Materials and methods In this study, we explored a putative T β4 protective role in lung damage by utilizing a well‐known in vivo model of lung fibrosis. C57 BL /6 mice were treated with bleomycin ( BLEO , 1 mg/kg) in the absence or presence of T β4 (6 mg/kg delivered intraperitoneally on the day of BLEO treatment and for two additional doses). After sacrifice 1 week later, measurement of fluid and collagen content in the lung, BALF analysis, myeloperoxidase (MPO) activity assay, lung histology and IHC were performed. Results Compared with BLEO ‐treated mice, BLEO ‐treated mice who received T β4 did not lose as much weight and had a higher survival rate. Moreover, BLEO ‐induced inflammation and lung damage were substantially reduced by T β4 treatment, as demonstrated by the significant reduction in oedema, total collagen content, lung infiltration by leucocytes, MPO activity in lung homogenates, and histological evidence of the ongoing lung fibrosis. Results of IHC show a strong reactivity for T β4 in the lung tissue of T β4‐treated mice. Conclusions This is the first report that shows a T β4 protective role in lung toxicity associated with BLEO in a mouse model. Future studies are needed to assess its putative antifibrotic properties.