Effects of different corticosteroid doses and durations on smoke inhalation-induced acute lung injury and pulmonary fibrosis in the rat

Abstract

Excessive inflammation induced by cytokine storm and coagulation disorders is considered the primary characteristic of smoke inhalation-induced acute lung injury (SI-ALI). Glucocorticoids such as methylprednisolone (MP) are commonly used to treat patients with inflammatory diseases; however, the management of ALI or acute respiratory distress syndrome (ARDS) remains controversial. We explored the effects of different MP doses and durations in a rat SI-ALI model. SI-ALI model rats had a high mortality rate and severe lung injury with proinflammatory, procoagulant, and pro-fibrotic changes. We found that a medium MP dose (4 mg/kg) markedly improved survival rates compared with low (0.4 mg/kg) and high (40 mg/kg) doses in the acute phase. A medium dose significantly attenuated lung injury, and reduced proinflammatory cytokine production and neutrophil infiltration into alveoli. Both medium and high MP doses improved coagulation and fibrinolysis conditions compared with low-dose MP. We also explored the effect of different durations of MP treatment on attenuating fibrotic changes in late-phase SI-ALI. Pro-fibrotic chemokine levels were gradually increased, followed by an increase in collagen and fibrin deposition after smoke inhalation. Three and 7-day MP treatments significantly attenuated this process, which was reflected by a reduction in pro-fibrotic chemokine levels. There was no significant difference between 3- and 7-day treatments. We report that a medium MP (4 mg/kg) dose significantly reduced inflammation and coagulation disorders, as well as acute-phase mortality. Three-day MP treatment may sufficiently attenuate fibrotic changes in late-phase SI-ALI.