Blocking IL-6 trans-Signaling Prevents High-Fat Diet-Induced Adipose Tissue Macrophage Recruitment but Does Not Improve Insulin Resistance

Abstract

The original version of this article included a misprint of the Gene Expression Omnibus (GEO) number for the microarray data reported in the paper. The actual accession number is GEO: GSE63761. In addition, the Supplemental Information was published with the Supplemental Experimental Procedures missing. Both of these errors have since been corrected online. The journal apologizes for any inconvenience.

Is the risk of cardiovascular disease altered with anti‐inflammatory therapies? Insights from rheumatoid arthritis

“…55 These sgp130Fc transgenic mice are protected from obesity-induced white adipose tissue macrophage accumulation without having an impact on circulating lipids. 56 Furthermore, sgp130Fc administration reduces atherosclerosis in high-fat-fed Ldlr −/− mice without altering body mass or the blood lipid profile, suggesting that sgp130Fc may be a therapeutic target for the treatment of atherosclerosis. 57 As bacterial infections and hyperlipidemia are major consequences of global IL-6 blockade in RA patients treated with tocilizumab, it is hypothesized that IL-6-trans-signaling antagonism with sgp130Fc may provide a more specific treatment option.…”

Delayed revascularization of islets after transplantation by IL‐6 blockade in pig to non‐human primate islet xenotransplantation model

“…[10][11][12] IL-6 is a pleiotropic factor, having good and bad impacts on many physiological processes. [13][14][15] For example, IL-6 has been shown to increase vascular endothelial growth factor and induce angiogenesis in a tumor model 16 and stimulate circulating blood-derived endothelial progenitor cell during angiogenesis in vitro. 17 In contrast, IL-6 has been reported to amplify activation of coagulation through up-regulation of tissue factor on innate immune cells and resulted in systemic inflammation in xenograft recipient (SIXR).…”

Inflammation and insulin resistance: New targets encourage new thinking

“…Any effort to target IL-6 to treat insulin resistance, would need to balance or discriminate between these different factors. One recent study by Kraakman et al [67] attempted to do this by targeting specifically IL-6 trans-signaling, whereby IL-6 is bound by soluble IL-6R in circulation and is targeted to inflammatory cells expressing gp130. Targeting this aspect of IL-6-signaling, but leaving membrane-bound IL-6R signaling intact, resulted in resolution of adipose tissue inflammation without exacerbation of obesity and insulin resistance [67].…”

“…One recent study by Kraakman et al [67] attempted to do this by targeting specifically IL-6 trans-signaling, whereby IL-6 is bound by soluble IL-6R in circulation and is targeted to inflammatory cells expressing gp130. Targeting this aspect of IL-6-signaling, but leaving membrane-bound IL-6R signaling intact, resulted in resolution of adipose tissue inflammation without exacerbation of obesity and insulin resistance [67]. However, although the negative consequences of targeting IL-6 signaling were prevented, this method was not sufficient to improve insulin sensitivity overall [67].…”

“…Targeting this aspect of IL-6-signaling, but leaving membrane-bound IL-6R signaling intact, resulted in resolution of adipose tissue inflammation without exacerbation of obesity and insulin resistance [67]. However, although the negative consequences of targeting IL-6 signaling were prevented, this method was not sufficient to improve insulin sensitivity overall [67].…”