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Delayed administration of recombinant plasma gelsolin improves survival in a murine model of severe influenza.


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.

SUBMITTER: Yang Z 

PROVIDER: S-EPMC6894358 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Delayed administration of recombinant plasma gelsolin improves survival in a murine model of severe influenza.

Yang Zhiping Z   Bedugnis Alice A   Levinson Susan S   DiNubile Mark M   Stossel Thomas T   Lu Quan Q   Kobzik Lester L  

F1000Research 20191106


<b>Background:</b> 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.   <b>Methods:</b> We evaluated delayed therapy with subcutaneous rhu-pGSN initiated 3 to 6 days after intra-nasal viral challen  ...[more]

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