The function of neutrophils in viral infections has long been established and studies have been done to examine the role of neutrophil extracellular traps (NETs). Further study and analysis of NETs in viral infections may reveal a new therapeutic target. Administration of ibuprofen and GS-561937, a fusion protein inhibitor (FPI), have been experimentally shown to decrease the severity of bovine respiratory syncytial virus (BRSV) infection. Our aims were to determine the effect of ibuprofen and FPI on NETs after BRSV infection as a monotherapy or combined therapy.

Methods

We conducted a randomized placebo-controlled trial of ibuprofen, FPI, or as a dual therapy initiated at 3 or 5 days after experimental infection with BRSV in 36 five to six-week-old Holstein calves (Bos Taurus). Lung tissue samples were collected and stained with antibodies conjugated with fluorescence dyes to visualize and quantify the NETs in situ. We estimated the average NETs in the sample lung tissue slides and compared the areas occupied by NETS within and between the treatment groups.

Results

There were significantly fewer NETs in the lung tissue from calves that were given ibuprofen and both ibuprofen and fusion protein inhibitor from day 3 post infection compared to the placebo group. Calves administered with ibuprofen, fusion protein inhibitor or both from day five had visually fewer NETs than the placebo but the difference was not significant.

Conclusion

BRSV can induce NET formation in vitro and in vivo. A combination of both drugs (Ibuprofen and FPI) resulted in less NETs observed in lung tissue of BRSV infected calves compared to the placebo or monotherapy groups.

中文翻译：

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中性粒细胞胞外陷阱 (NETs) 在牛呼吸道合胞病毒感染模型中联合使用抗病毒和非甾体抗炎治疗的随机对照试验

中性粒细胞在病毒感染中的功能早已确立，并且已经进行了研究以检查中性粒细胞胞外陷阱 (NET) 的作用。对病毒感染中 NETs 的进一步研究和分析可能会揭示一个新的治疗靶点。布洛芬和融合蛋白抑制剂 (FPI) GS-561937 的给药已被实验证明可降低牛呼吸道合胞病毒 (BRSV) 感染的严重程度。我们的目的是确定布洛芬和 FPI 在 BRSV 感染后作为单一疗法或联合疗法对 NETs 的影响。

方法

我们在 36 头 5 至 6 周龄的荷斯坦小牛 (Bos Taurus) 中进行了布洛芬、FPI 或作为双重治疗的随机安慰剂对照试验，试验性感染 BRSV 后 3 或 5 天开始。收集肺组织样本并用与荧光染料结合的抗体染色，以原位可视化和量化 NET。我们估计了样本肺组织载玻片中的平均 NETs，并比较了治疗组内和治疗组之间 NETS 占据的区域。

结果

与安慰剂组相比，从感染后第 3 天开始，给予布洛芬和布洛芬和融合蛋白抑制剂的小牛肺组织中的 NET 显着减少。从第 5 天开始，给予布洛芬、融合蛋白抑制剂或两者的小牛的 NET 明显少于安慰剂，但差异不显着。

结论

BRSV 可以在体外和体内诱导 NET 形成。与安慰剂或单一疗法组相比，两种药物（布洛芬和 FPI）的组合导致在 BRSV 感染小牛的肺组织中观察到的 NETs 较少。