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

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F1000Res. 2019 Nov 6;8:1860. doi: 10.12688/f1000research.21082.1. eCollection 2019. Delayed administration of recombinant plasma gelsolin improves survival in a murine model of severe influenza.

Yang Z¹, Bedugnis A¹, Levinson S², DiNubile M², Stossel T², Lu Q¹, Kobzik L¹.
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1 Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, 02115, USA. 2 BioAegis Therapeutics, North Brunswick, NJ, 07960, USA.

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.
Copyright: ? 2019 Yang Z et al.


KEYWORDS:

host-directed; immunomodulation; influenza; plasma gelsolin; pneumonia

PMID: 31824672 PMCID: PMC6894358 DOI: 10.12688/f1000research.21082.1
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