Neutrophil extracellular traps (NETs) in a randomized controlled trial of a combination of antiviral and nonsteroidal anti-inflammatory treatment in a bovine model of respiratory syncytial virus infection.

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. 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. 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. 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.

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