Inhaled Nitric Oxide Therapy Fails to Improve Outcome in Experimental Severe Influenza

Darwish, Ilyse; Miller, Chris; Kain, Kevin C.; Liles, W. Conrad

As gaseous NO (gNO) at high concentrations has been shown to decrease the viral load of infected cells in vitro (Miller C, personal communication), we examined whether iNO could reduce the viral load of influenza virus-infected mice. iNO was administered starting 1 hour prior to influenza WSN/33 infection and continued either continuously at 80 ppm or in-termittently at 160 ppm for 30 min every 3.5 hours until mouse lungs were harvested at peak influenza viral load in the lungs (determined to be day 5 post-infection based on preliminary studies, data not shown). Since iNO was administered both prior to and for 5 days post-infection, we were able to test whether iNO at intermediate (80 ppm) or high concentration (160 ppm) could prevent either viral entry or viral replication in vivo, and thereby reduce viral load. Continuous iNO at 80 ppm, intermittent iNO at 160 ppm, and compressed room air administration yielded similar lung viral loads of infected mice on day 5 post-infection ( Fig. 3a and b, respectively) . Therefore, both continuous and intermittent iNO administration failed to reduce lung viral load of infected mice, compared to infected control mice administered compressed room air.