Abstract
Background: Host-derived inflammatory responses contribute to the morbidity and mortality of severe influenza, suggesting that immunomodulatory therapy may improve outcomes. The normally circulating protein, human plasma gelsolin, is available in recombinant form (rhu-pGSN) and has beneficial effects in a variety of pre-clinical models of inflammation and injury. Methods: We evaluated delayed therapy with subcutaneous rhu-pGSN initiated 3 to 6 days after intra-nasal viral challenge in a mouse model of influenza A/PR/8/34. Results: Rhu-pGSN administered starting on day 3 or day 6 increased survival (12-day survival: 62 % vs 39 %, pGSN vs vehicle; p < 0.00001, summary of 18 trials), reduced morbidity, and decreased pro-inflammatory gene expression. Conclusions: Rhu-pGSN improves outcomes in a highly lethal influenza model when given after a clinically relevant delay.
Highlights
Seasonal influenza continues to be a cause of substantial morbidity and mortality
This article is included in the Emerging Diseases and Outbreaks gateway
There is a fear that a new virulent influenza strain could cause high death rates, similar to those seen during the 1918 pandemic1
Summary
Seasonal influenza continues to be a cause of substantial morbidity and mortality. There is a fear that a new virulent influenza strain could cause high death rates, similar to those seen during the 1918 pandemic. The pathogenesis of influenza involves dysregulated and injurious host inflammatory responses. The pathogenesis of influenza involves dysregulated and injurious host inflammatory responses4–6 This observation suggests that better inflammation control with immunomodulatory therapy may be able to reduce the morbidity and mortality seen in severe infections. Host-derived inflammatory responses contribute to the morbidity and mortality of severe influenza, suggesting that immunomodulatory therapy may improve outcomes. The normally circulating protein, human plasma gelsolin, is available in recombinant form (rhu-pGSN) and has beneficial effects in a variety of pre-clinical models of inflammation and injury
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