摘要

It is well documented that, besides reducing blood LDL lipoproteins, HMG-CoA reductase inhibitors (statins) also suppress inflammatory markers and improve survival in sepsis. These beneficial effects can be at least partly explained by their capacity to inhibit the release of IL-6, which is generally regarded as a proinflammatory cytokine, although a variety of other actions including anti-inflammatory have been reported for this cytokine under various circumstances. In quantitative terms, IL-6 release is a major response of the skeletal muscle to various environmental stimuli and since muscle represents 40% of the body weight it can substantially contribute to the IL-6 blood level. The aim of our study was to provide more detailed insight into the effects of statins on the IL-6 release from the human skeletal muscle. Studying time and concentration dependency of the constitutive and lipopolysaccharide (LPS)-stimulated IL-6 release from the cultured human myotubes we found that 48 h pre-treatment with atorvastatin (AT) significantly inhibits constitutive IL-6 secretion at high (1 mu M) and supra (10 mu M and 100 mu M) therapeutic concentrations. At these AT concentrations, LPS-stimulated IL-6 secretion was also significantly reduced by 48 h AT co-treatment or pre-treatment, but not by post-treatment; therapeutic (0.1 mu M) AT concentration was efficient only in pre-treatment but not in co-treatment or post-treatment LPS protocols. This information is an important clue for the investigations of the molecular mechanisms underlying AT effects and its therapeutic applications.

  • 出版日期2012-1