Human Recombinant Interferon-α2a and Interferon-αA/D Have Different Effects on Bleomycin-Induced Lung Injury

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Abstract
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)-α 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-α (IFN-αA/D and IFN-α2a) 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-α preparations, IFN-αA/D or IFN-α2a 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-α2a; IT Bleo and intraperitoneal IFN-αA/D; IT saline and intraperitoneal IFN-αA/D or IFN-α2a; 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-α2a treatment caused a significant rise in BAL lymphocytes and in cellularity and fibrosis fractions in lung tissue. In contrast, IFN-αA/D treatment had no effect on Bleo-induced lung injury. Conclusion: IFN-α may enhance Bleo-induced lung injury but this effect varies with different IFN preparations.