Glucocorticoid suppresses neutrophil activation in ventilator-induced lung injury.

Objective: To investigate, in a rat model, the role of the Mac1/ICAM-1 pathway and the anti-inflammatory activity of steroid in ventilator-induced lung injury. Design: Prospective, randomized controlled study. Setting: Animal investigation using Wistar rats. Intervention: Rats in three randomly assigned groups of 18, a total of 54 animals, were subject to the following: Two groups received high peak inspiratory pressure (35 cm H 2 O) ventilation after pretreatment with methylprednisolone (high-methylprednisolone group) or pretreatment with methylprednisolone vehicle (high-vehicle group). The third group of animals received low peak inspiratory pressure (7 cm H 2 O) ventilation after pretreatment with methylprednisolone vehicle (low-vehicle group). Except for animals previously killed to establish baseline values, after 40 mins of mechanical ventilation, the animals in each group were killed. Some animals provided histological samples, and the rest received total lung lavage. Measurement: We measured flow cytometry of lavage fluid, cell counts of tissue samples, and pressure-volume curves before and after mechanical ventilation. Results: In the groups that received high peak inspiratory pressure ventilation, both the number of neutrophils that infiltrated the lungs and the expression of Mac-1 and ICAM-1 on neutrophils and macrophages increased significantly more than in the low-vehicle group. Static lung compliance was reduced in the high peak inspiratory pressure groups. In the high peak inspiratory pressure groups, there were significantly fewer neutrophils in samples from the high-methylprednisolone group (0.412 ± 0.1 x 10 5 ) than from the high-vehicle group (1.10 ± 0.1 x 10 5 ; p <.05). The high-vehicle group showed greater expression of CD11 b on neutrophils, but this was significantly decreased by methylprednisolone (mean fluorescence intensity: high-vehicle, 118.4 ± 34.3; high-methylprednisolone, 25.8 ± 4.2; p <.05). The lung mechanics measured by pressure-volume curve analysis were deteriorated less in the high-methylprednisolone group. Conclusion: Our study suggests that a neutrophil-endothelium interaction via the Mac-1/ICAM-1 pathway is involved in the activation and recruitment of neutrophils in ventilator-induced lung injury. Activation and recruitment of neutrophils were lessened by pretreatment with methylprednisolone, which might have contributed to the improvement of lung dysfunction after mechanical ventilation.