In vivo vitamin E administration attenuates interleukin-6 and interleukin-1beta responses to an acute inflammatory insult in mouse skeletal and cardiac muscle

Exp Physiol. 2008 Dec;93(12):1263-72. doi: 10.1113/expphysiol.2008.043190. Epub 2008 Jun 27.


Antioxidants are associated with reduced pro-inflammatory cytokine expression in immune cells and isolated tissues; however, no studies have examined whether short-term vitamin E administration is associated with reduced lipopolysaccharide (LPS)-induced cytokine expression in mouse skeletal and cardiac muscle, in vivo. These experiments tested the hypothesis that vitamin E administration attenuates nuclear factor kappaB (NF-kappaB), IL-6, IL-1beta and tumour necrosis factor alpha (TNFalpha) responses in skeletal and cardiac muscle to an inflammatory challenge induced by systemic LPS. We compared IL-6, IL-1beta and TNFalpha mRNA and protein, activated NF-kappaB and total oxidized proteins in skeletal and cardiac muscle 4 or 24 h after saline or LPS injection in mice receiving vitamin E or placebo for 3 days prior to the insult. Skeletal and cardiac IL-6 mRNA and protein were significantly elevated by LPS in both groups, but responses were significantly lower in vitamin E- compared with placebo-treated mice. In skeletal and cardiac muscle, LPS increased IL-1beta mRNA and protein in placebo- but not vitamin E-treated mice. Lipopolysaccharide-induced levels of cardiac IL-1beta mRNA and protein and skeletal IL-1beta mRNA were lower with vitamin E than placebo. Lipopolysaccharide-induced NF-kappaB activation and increases in total oxidized proteins were attenuated with vitamin E compared with placebo in both tissues. Vitamin E decreased LPS-induced increases in plasma IL-1beta but not IL-6 compared with placebo. The major results provide the first in vivo evidence that short-term vitamin E administration reduces IL-6 and IL-1beta responses to LPS in skeletal and cardiac muscle and prevents LPS-induced increases in NF-kappaB activation and total oxidized proteins.

Publication types

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

MeSH terms

  • Acute Disease
  • Animals
  • Anti-Inflammatory Agents / administration & dosage*
  • Antioxidants / administration & dosage*
  • Disease Models, Animal
  • Inflammation / chemically induced
  • Inflammation / immunology
  • Inflammation / prevention & control*
  • Interleukin-1beta / blood
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism*
  • Interleukin-6 / blood
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism*
  • Lipopolysaccharides
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / immunology
  • NF-kappa B / metabolism
  • Papillary Muscles / drug effects*
  • Papillary Muscles / immunology
  • Protein Carbonylation / drug effects
  • RNA, Messenger / metabolism
  • Time Factors
  • Tumor Necrosis Factor-alpha / metabolism
  • Vitamin E / administration & dosage*


  • Anti-Inflammatory Agents
  • Antioxidants
  • Interleukin-1beta
  • Interleukin-6
  • Lipopolysaccharides
  • NF-kappa B
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Vitamin E