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

F1000Res. 2019 Nov 6;8:1860. doi: 10.12688/f1000research.21082.2. eCollection 2019.

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.

Keywords: host-directed; immunomodulation; influenza; plasma gelsolin; pneumonia.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Disease Models, Animal
  • Gelsolin* / therapeutic use
  • Humans
  • Inflammation
  • Influenza, Human* / drug therapy
  • Mice
  • Recombinant Proteins* / therapeutic use
  • Survival Analysis

Substances

  • Gelsolin
  • Recombinant Proteins