BACKGROUND Given the role that T lymphocytes play on the pathogenesis of allergic asthma, drugs targeting Th2 and Th17 cells may be a hopeful therapeutic strategy. This study aimed to evaluate the effect of rosuvastatin treatment on cytokine production and lung inflammation in allergic asthma. METHODS The animals were assigned into control (C), asthmatic (A), hyperlipidemic (H), asthmatic-hyperlipidemic (AH), rosuvastatin (40 mg/kg/day intraperitoneally, for 3 weeks)-treated asthmatic (AR), rosuvastatin-treated hyperlipidemic (HR) and rosuvastatin-treated asthmatic-hyperlipidemic (AHR) groups (n = 6 in each group). The levels of IL-4, IFN-γ and IL-17, total and differential WBC counts in bronchoalveolar lavage fluid (BALF), Th1/Th2 balance, and pathological changes were evaluated. RESULTS The BALF level of IL-4 in A, H and AH groups, and IL-17A in A and AH groups were significantly higher than that in C group (p < 0.05 to p < 0.001). IFN-γ level and Th1/Th2 balance (IFN‑γ/IL-4 ratio) in A and AH groups were significantly decreased (p < 0.05 to p < 0.01). Inflammatory cells infiltration, muscle hypertrophy and emphysema were also observed in A and AH groups. The BALF levels of IL-4 in AR, HR and AHR groups, IFN-γ level in HR group, and IL-17A level in AR and AHR groups showed a significant improvement compared to that of A, H and AH groups (p < 0.05 to p < 0.001). Rosuvastatin treatment increased Th1/Th2 balance in all treated groups (p < 0.05 to p < 0.01), decreased total WBC counts, neutrophilia, eosinophilia and lung inflammation in AR and AHR groups, and improved muscle hypertrophy and emphysema in AHR group. CONCLUSIONS Rosuvastatin treatment improved lung pathological changes by suppression of Th2 and Th17-mediated cytokines which was unrelated to its lipid-lowering activity. Therefore, rosuvastatin might be a candidate immunomodulatory drug for treatment of patients with allergic asthma.

中文翻译：

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瑞舒伐他汀抑制哮喘、高脂血症和哮喘-高脂血症大鼠模型中细胞因子的产生和肺部炎症

背景 鉴于 T 淋巴细胞在过敏性哮喘发病机制中的作用，靶向 Th2 和 Th17 细胞的药物可能是一种有希望的治疗策略。本研究旨在评估瑞舒伐他汀治疗对过敏性哮喘中细胞因子产生和肺部炎症的影响。方法 将动物分为对照 (C)、哮喘 (A)、高脂血症 (H)、哮喘-高血脂 (AH)、瑞舒伐他汀（40 mg/kg/天腹腔注射，持续 3 周）-治疗哮喘 (AR)、瑞舒伐他汀-治疗的高脂血症 (HR) 组和瑞舒伐他汀治疗的哮喘高脂血症 (AHR) 组（每组 n = 6）。评估了 IL-4、IFN-γ 和 IL-17 的水平、支气管肺泡灌洗液 (BALF) 中的 WBC 总数和分类计数、Th1/Th2 平衡和病理变化。结果A、H、AH组IL-4的BALF水平，A组和AH组的IL-17A和IL-17A显着高于C组（p < 0.05至p < 0.001）。A 组和 AH 组的 IFN-γ 水平和 Th1/Th2 平衡（IFN-γ/IL-4 比值）显着降低（p < 0.05 至 p < 0.01）。A组和AH组还观察到炎性细胞浸润、肌肉肥大和肺气肿。AR、HR、AHR组BALF中IL-4水平、HR组IFN-γ水平、AR和AHR组IL-17A水平均较A、H、AH组显着改善（p < 0.05 至 p < 0.001）。瑞舒伐他汀治疗增加了所有治疗组的 Th1/Th2 平衡（p < 0.05 至 p < 0.01），减少 AR 和 AHR 组的总 WBC 计数、中性粒细胞增多、嗜酸性粒细胞增多和肺部炎症，并改善 AHR 组的肌肉肥大和肺气肿。结论瑞舒伐他汀治疗通过抑制与其降脂活性无关的 Th2 和 Th17 介导的细胞因子来改善肺部病理变化。因此，瑞舒伐他汀可能是治疗过敏性哮喘患者的候选免疫调节药物。