Plasma gelsolin is a marker and therapeutic agent in animal sepsis

Crit Care Med. 2007 Mar;35(3):849-55. doi: 10.1097/01.CCM.0000253815.26311.24.


Objective: Plasma gelsolin is a circulating actin-binding protein that serves a protective role against tissue injuries. Depletion of plasma gelsolin in systemic inflammation may contribute to adverse outcomes. We examined the role of plasma gelsolin in animal models of sepsis.

Design: Animal and laboratory experiments.

Setting: Academic research laboratory.

Subjects: Adult male mice.

Interventions: Mice subjected to endotoxin or cecal ligation and puncture (CLP) were treated with exogenous plasma gelsolin or placebo.

Measurements and main results: We document the depletion of plasma gelsolin (25-50% of normal) in murine models of sepsis associated with the presence of circulating actin within 6 hrs of septic challenge. Repletion of plasma gelsolin leads to solubilization of circulating actin aggregates and significantly reduces mortality in endotoxemic mice (survival rates were 88% in the gelsolin group vs. 0% in the saline group, p < .001) and in CLP-challenged mice (survival rates were 30% in the gelsolin group vs. 0% in the saline group, p = .001). Plasma gelsolin repletion also shifted the cytokine profile of endotoxemic mice toward anti-inflammatory (plasma interleukin-10 levels were 205 +/- 108 pg/mL in the gelsolin group vs. 39 +/- 29 pg/mL in the saline group, p = .02).

Conclusions: We propose that circulation of particulate actin is a marker for sepsis-induced cell injury, that plasma gelsolin has a crucial protective role in sepsis, and that gelsolin replacement represents a potential therapy for this common lethal condition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / blood
  • Animals
  • Cytokines / blood
  • Disease Models, Animal
  • Endotoxemia / blood*
  • Endotoxemia / drug therapy*
  • Endotoxemia / mortality
  • Escherichia coli
  • Gelsolin / blood*
  • Gelsolin / therapeutic use*
  • Lipopolysaccharides
  • Male
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Peritonitis / blood
  • Peritonitis / drug therapy
  • Peritonitis / mortality
  • Shock, Septic / blood*
  • Shock, Septic / drug therapy*
  • Shock, Septic / mortality
  • Survival Rate
  • Toll-Like Receptor 4 / genetics


  • Actins
  • Cytokines
  • Gelsolin
  • Lipopolysaccharides
  • Toll-Like Receptor 4