Atorvastatin modulates constitutive and lipopolysaccharide induced IL-6 secretion in precursors of human skeletal muscle

Abstract

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 μM) and supra (10 μM and 100 μM) 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 μM) 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.

Neostigmine modulates tularemia progression in BALB/c mice

“…We hypothesize that after inhibition of the blood AChE by neostigmine, increasing level of blood acetylcholine activates the cholinergic anti-inflammatory pathway. Though we have no direct evidence of neostigmine implication in the cholinergic anti-inflammatory pathway, the proved decreases of IFN-and IL-6 in an indirectly proportionally dose response manner confirm the hypothesis when immunological meaning of the markers is considered (Golicnik et al, 2012). Aggravated mortality in course of tularemia is another plausible proof confirming the hypothesis as well.…”

Cytokine Response of Cultured Skeletal Muscle Cells Stimulated with Proinflammatory Factors Depends on Differentiation Stage

“…All donors gave their written informed consent. Preparation of primary culture of human skeletal muscle cells was performed as previously described [31–34]. Briefly, muscle samples were cleaned of connective and adipose tissue, cut into small pieces, and then trypsinised for 30 minutes in Earle's Balanced Salt Solution supplemented with trypsin-EDTA at 37°C.…”