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

Abstract

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.