Human recombinant inteuferon-α2a and interferon-αA/D have different effects on bleomycin-induced lung injury

Background: Bleomycin (Bleo)-induced lung injury in mice serves as an animal model of pulmonary fibrosis. The pathogenesis of pulmonary fibrosis remains unclear, but it comprises both inflammatory and fibrotic components. The cytokine interferon (IFN)-alpha is produced by macrophages and may modulate both fibrogenesis and the determination of T lymphocyte phenotype in pulmonary fibrosis. Objective: To investigate the effect of two preparations of recombinant IFN-alpha (IFN-alphaA/D and IFN-alpha 2a) on Bleo-induced lung injury in C57BL/6 mice. Methods: Mice were treated by a single intratracheal (IT) instillation of 0.06 mg of Bleo in 0.1 ml of saline or saline alone. One of two different IFN-alpha preparations, IFN-alpha AID or IFN-alpha 2a in saline, or saline alone were administered by daily intraperitoneal injections starting 1 day prior to IT instillation: The treatment groups were as follows: IT Bleo and intraperitoneal saline; IT Bleo and intraperitoneal IFN-alpha 2a; IT Bleo and intraperitoneal IFN-alphaA/D; IT saline and intraperitoneal IFN-alpha AID or IFN-alpha 2a; IT saline and intraperitoneal saline. The animals were sacrificed 14 days after IT instillation. Lung injury was evaluated by total and differential cell count in bronchoalveolar lavage (BAL) fluid, by a semiquantitative morphological index of lung injury and a quantitative image analysis of cellularity and fibrosis fraction and by biochemical analysis of lung hydroxyproline content. Results: In Bleo-treated mice, IFN-alpha 2a treatment caused a significant rise in BAL lymphocytes and in cellularity and fibrosis fractions in lung tissue. In contrast, IFN-alphaA/D treatment had no effect on Bleo-induced lung injury. Conclusion: IFN-alpha may enhance Bleo-induced lung injury but this effect varies with different IFN preparations. Copyright (C) 2001 S. Karger AG, Basel.