IL-6 and metabolism—new evidence and new questions

Excerpt

Does the cytokine IL-6 play a role in the regulation of metabolism? From a rather unexciting existence as a lacklustre, but dependable player in the textbook version of the inflammatory response, IL-6 has recently taken centre stage in the search for culprits underlying the inflammatory component of the metabolic syndrome. Reduced insulin action following in vitro exposure of cultured adipose and hepatocyte cells to IL-6 has been submitted as evidence strongly implicating IL-6 in the direct induction of insulin resistance [1‐4]. In contrast, data indicating that IL-6 deficiency in mice leads to obesity and insulin resistance provides evidence against a causative effect of IL-6 in insulin resistance [5]. Furthermore, contraction-stimulated release of IL-6 from skeletal muscle has been coupled to positive metabolic effects associated with exercise, such as the enhancement of insulin sensitivity [6]. Numerous explanations for these two divergent opinions have been put forward, including differences in model systems, chronic versus pulsatile exposure, and in vitro vs in vivo effects [7, 8]. In this issue of Diabetologia, Franckhauser and colleagues add another piece to the puzzle [9]. In an elegant set of experiments, circulating IL-6 levels were increased by introducing a cytomegalovirus-driven Il6 gene into several skeletal muscle groups in the mouse hindlimb by electrotransfer. This gene manipulation results in a rapid (within days) and sustained elevation of circulating IL-6 levels in an in vivo system. …