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Hemoglobin increases mortality from bacterial endotoxin

D Su1, R I Roth, M Yoshida

  • 1Department of Laboratory Medicine, University of California School of Medicine, Department of Veterans Affairs Medical Center, San Francisco 94121, USA.

Infection and Immunity
|April 1, 1997
PubMed
Summary
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Cell-free hemoglobin (Hb) administration significantly increases mortality in lipopolysaccharide (LPS)-induced sepsis in mice. This finding raises concerns for Hb-based blood substitutes in patients with infections.

Area of Science:

  • Biomedical Science
  • Toxicology
  • Pharmacology

Background:

  • Cell-free hemoglobin (Hb) is investigated as an erythrocyte substitute.
  • Hb binds endotoxin (lipopolysaccharide, LPS), increasing its biological activity in vitro.
  • Gram-negative bacterial infections cause significant morbidity and mortality due to LPS.

Purpose of the Study:

  • To investigate the effect of cell-free Hb on LPS-mediated mortality in a mouse model.
  • To determine if Hb administration influences the survival rates of animals exposed to LPS.

Main Methods:

  • Intravenous infusion of Hb into mice before, during, or after intraperitoneal LPS injection.
  • Observation of mortality rates at 24 and 48 hours post-LPS administration.
  • Evaluation of different doses of Hb and LPS, and various Hb modifications.

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Main Results:

  • Hb administration substantially increased LPS-related mortality from <5% to 50-70% at 24 hours and 50% to 60-90% at 48 hours.
  • Mortality enhancement was observed across a range of LPS doses and was dose-dependent on Hb.
  • Various forms of human and bovine Hb, including cross-linked variants, enhanced LPS-mediated mortality.

Conclusions:

  • Cell-free Hb significantly exacerbates LPS-induced mortality in mice.
  • Potential mechanisms include depressed reticuloendothelial cell function.
  • Hb-based blood substitutes may increase the risk of severe sepsis in clinical settings.