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September 2, 1997Circulation

Modulation of Cytokine Production and Protection Against Lethal Endotoxemia by the Cardiac Glycoside Ouabain

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Authors

AMAkira MatsumoriKOKoh OnoRNRyosuke Nishio

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Overview

Ouabain shows context-dependent cytokine effects and endotoxemia protection in models; leaves open relevance to glycoside therapy in heart failure.

Key Points

  • To determine whether the cardiac glycoside ouabain modulates the production of inflammatory cytokines in vitro and protects against endotoxin-induced lethality in vivo.
  • Cultured human peripheral blood mononuclear cells (PBMC) with or without ouabain in the presence or absence of lipopolysaccharide (LPS), using kinase inhibitors to probe intracellular pathways.
  • Administered ouabain to LPS-treated mice to evaluate survival rates and circulating levels of IL-6 and TNF-alpha in vivo.
  • In resting human PBMC, ouabain induced mRNA transcription and protein release of IL-1beta, IL-6, and TNF-alpha, mediated via protein kinase C and tyrosine kinase pathways.
  • In LPS-stimulated human PBMC, ouabain conversely suppressed the production of IL-6 and TNF-alpha.
  • In vivo, ouabain reduced circulating IL-6 and TNF-alpha concentrations and protected mice against LPS-induced lethal toxicity.

Cite This Study

Matsumori et al. (1997) studied this question.

synapsesocial.com/papers/6a712ca435aa2c282ce27d1dhttps://doi.org/10.1161/01.cir.96.5.1501
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