Delayed Administration of Recombinant Plasma Gelsolin Improves Survival in a Murine Model of Penicillin-Susceptible and Penicillin-Resistant Pneumococcal Pneumonia

J Infect Dis. 2019 Sep 26;220(9):1498-1502. doi: 10.1093/infdis/jiz353.

Abstract

Therapy to enhance host immune defenses may improve outcomes in serious infections, especially for antibiotic-resistant pathogens. Recombinant human plasma gelsolin (rhu-pGSN), a normally circulating protein, has beneficial effects in diverse preclinical models of inflammation and injury. We evaluated delayed therapy (24-48 hours after challenge) with rhu-pGSN in a mouse model of pneumococcal pneumonia. rhu-pGSN without antibiotics increased survival and reduced morbidity and weight loss after infection with either penicillin-susceptible or penicillin-resistant pneumococci (serotypes 3 and 14, respectively). rhu-pGSN improves outcomes in a highly lethal pneumococcal pneumonia model when given after a clinically relevant delay, even in the setting of antimicrobial resistance.

Keywords: antibiotic-resistance; immunomodulation; plasma gelsolin; pneumonia.

Publication types

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

MeSH terms

  • Animals
  • Disease Models, Animal
  • Gelsolin / administration & dosage*
  • Immunologic Factors / administration & dosage*
  • Male
  • Mice
  • Pneumonia, Pneumococcal / drug therapy*
  • Pneumonia, Pneumococcal / pathology
  • Recombinant Proteins / administration & dosage
  • Survival Analysis
  • Treatment Outcome
  • Weight Loss

Substances

  • Gelsolin
  • Immunologic Factors
  • Recombinant Proteins