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

摘要

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 κB(NF-κB), IL-6, IL-1β and tumour necrosis factor α (TNFα) responses in skeletal and cardiac muscle to an inflammatory challenge induced by systemic LPS. We compared IL-6, IL-1β and TNFα mRNA and protein, activated NF-κB 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-1β mRNA and protein in placebo- but not vitamin E-treated mice. Lipopolysaccharide-induced levels of cardiac IL-1β mRNA and protein and skeletal IL-1β mRNA were lower with vitamin E than placebo. Lipopolysaccharide-induced NF-κB 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-1β 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-1β responses to LPS in skeletal and cardiac muscle and prevents LPS-induced increases in NF-κB activation and total oxidized proteins.