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Comparison of ribavirin and oseltamivir in reducing mortality and lung injury in mice infected with mouse adapted A/California/04/2009 (H1N1)

机译：利巴韦林和奥司他韦在降低小鼠适应性A / California / 04/2009（H1N1）感染小鼠的死亡率和肺损伤中的比较

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Aim: To compare the efficacy of ribavirin and oseltamivir in reducing mortality, lung injury and cytokine response profile in pandemic influenza H1N1 (2009) infection. Main methods: We assessed survival, weight loss, lung viral load (by RT-PCR), lung injury (by protein content in bronchoalveolar lavage), and inflammation (cell counts, differentials and cytokines in the bronchoalveolar lavage) in BALB/c mice after infection with mouse-adapted pandemic influenza strain A/California/04/2009. Key findings: Our results indicate that ribavirin (80 mg kg - 1) and oseltamivir (50 mg kg - 1) are equally effective in improving survival (100% vs. 0% in water treated controls), while ribavirin proved to be more effective in significantly preventing weight loss. Both drugs diminished the injury of the alveolar-capillary barrier by decreasing the protein detected in the BAL to baseline levels, and they were also equally effective in reduction lung viral loads by 100-fold. Administration of either drug did not decrease the amount of inflammatory infiltrate in the lung, but ribavirin significantly reduced the percentage comprised of lymphocytes. This study shows that these antivirals differentially regulate inflammatory cytokines and chemokines with ribavirin significantly reducing most of the cytokines/chemokines measured. Ribavirin treatment leads to a Th1 cytokine response while oseltamivir leads to a Th2 cytokine response with significant increase in the levels of the anti-inflammatory cytokine IL-10. Significance: This study reveals new mechanistic insights in the way that ribavirin and oseltamivir exert their antiviral activity and supports the theory that ribavirin could potentially serve as an efficacious therapeutic alternative for oseltamivir resistant pandemic H1N1 strains.
机译：目的：比较利巴韦林和奥司他韦在大流行性流感H1N1（2009）感染中降低死亡率，肺损伤和细胞因子反应谱的功效。主要方法：我们评估了BALB / c小鼠的存活率，体重减轻，肺病毒载量（通过RT-PCR），肺损伤（通过支气管肺泡灌洗液中的蛋白质含量）和炎症（支气管肺泡灌洗液中的细胞计数，差异和细胞因子）。适应小鼠的大流行性流感毒株A /加利福尼亚04/2009。主要发现：我们的结果表明，利巴韦林（80 mg kg-1）和奥司他韦（50 mg kg-1）在提高生存率方面同样有效（在水处理对照组中为100％比0％），而利巴韦林被证明更有效在显着防止体重减轻方面。两种药物都通过将BAL中检测到的蛋白质降低到基线水平来减少肺泡-毛细血管屏障的损伤，并且它们同样有效地将肺病毒载量降低了100倍。两种药物的使用均未减少肺中炎性浸润的量，但利巴韦林显着降低了淋巴细胞的百分比。这项研究表明，这些抗病毒药物通过利巴韦林差异调节炎症细胞因子和趋化因子，从而显着减少了所测的大多数细胞因子/趋化因子。利巴韦林治疗可导致Th1细胞因子应答，而奥司他韦则可导致Th2细胞因子应答，且抗炎细胞因子IL-10的水平显着增加。意义：这项研究揭示了利巴韦林和奥司他韦发挥抗病毒活性的方式的新机制，并支持了利巴韦林可能作为耐奥司他韦大流行H1N1病毒株的有效治疗选择的理论。

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