Department of Pulmonary and Critical Care Medicine, 6(th) Medical Center of Chinese PLA General Hospital, 100033 Beijing, China; Department of Pulmonary and Critical Care Medicine, Chinese PLA General Hospital & Postgraduate Medical School, 100039 Beijing, China.
Department of Pulmonary and Critical Care Medicine, 6(th) Medical Center of Chinese PLA General Hospital, 100033 Beijing, China.
Int Immunopharmacol. 2019 Jun;71:392-403. doi: 10.1016/j.intimp.2019.03.051. Epub 2019 Apr 2.
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.
细胞因子风暴和凝血功能障碍引起的过度炎症被认为是吸入性烟雾导致急性肺损伤（SI-ALI）的主要特征。甲泼尼龙（MP）等糖皮质激素常用于治疗炎症性疾病患者；然而，ALI 或急性呼吸窘迫综合征（ARDS）的治疗仍存在争议。我们在大鼠 SI-ALI 模型中探索了不同 MP 剂量和持续时间的影响。SI-ALI 模型大鼠死亡率高，肺损伤严重，具有促炎、促凝和促纤维化变化。我们发现，与低（0.4mg/kg）和高（40mg/kg）剂量相比，中剂量（4mg/kg）MP 在急性期显著提高了生存率。中剂量显著减轻了肺损伤，并减少了促炎细胞因子的产生和中性粒细胞向肺泡的浸润。与低剂量 MP 相比，中剂量和高剂量 MP 均改善了凝血和纤溶状况。我们还探讨了不同 MP 治疗持续时间对减轻晚期 SI-ALI 纤维化变化的影响。趋化因子水平逐渐升高，随后吸入烟雾后胶原和纤维蛋白沉积增加。3 天和 7 天的 MP 治疗显著减轻了这一过程，表现为促纤维化趋化因子水平降低。3 天和 7 天的治疗之间没有显著差异。我们报告称，中剂量 MP（4mg/kg）显著减轻了炎症和凝血功能障碍，以及急性期死亡率。3 天的 MP 治疗可能足以减轻晚期 SI-ALI 的纤维化变化。
