Effect of immunomodulators on bleomycin-induced lung injury

Background: The role of lymphocytes and their subpopulations in lung fibros is is as yet unclear. Objective: To define the role of immunomodulation in bleomycin-induced inflammatory fibrotic lung injury, by testing the effect of two known Th1 inhibitors: linomide and pentoxifylline. Methods: C57BL/6 mice were treated by a single intratracheal instillation of 0.06 mg bleomyc in in 0.01 ml saline or saline alone. Treatment groups included: (1) intrat racheal bleomycin and daily treatment with linomide or pentoxifylline; (2) intratracheal bleomycin and daily water; (3) intratracheal saline and daily linomide or pentoxifylline; (4) intratracheal saline and daily water. Lino mide and pentoxifylline were available per os in the drinking water from 1 day prior to intratracheal instillation. Animals were studied 14 days after intratracheal instillation. Lung injury was evaluated by total and differe ntial cell count in bronchoalveolar lavage fluid, by a semiquantitative mor phological index of lung injury and a quantitative image analysis of cellul arity, fibrosis fraction and alveolar wall area fraction, and by biochemica l analysis of lung hydroxyproline content. Results: Linomide or pentoxifyll ine did not cause any lung injury in saline-treated control mice. Overt sig ns of lung injury were apparent in bleomycin-treated mice. These changes we re not affected by daily treatment with linomide or pentoxifylline, which w ere given in the highest tolerable dose. Conclusion: This study does not su pport the use of linomide or pentoxifylline to prevent or ameliorate lung f ibrosis and may suggest that drug-induced differentiation of T lymphocytes into Th1/th2 subpopulations does not affect the evolution of bleomycin-indu ced lung injury.