The pro-inflammatory molecule interleukin 6 (IL-6) may have an unexpected role in limiting the chronic, low-grade inflammatory state associated with obesity, according to a report published in Nature Immunology.
Obesity is associated with immune cell infiltration and activation in fat tissue as well as systemic elevation of pro-inflammatory cytokines. This leads to the development of insulin resistance and ultimately to overt type 2 diabetes. Jens Bruning and colleagues show that mice with an inactivated IL-6 receptor (IL-6R) gene, specifically in myeloid cells, display exaggerated deterioration of glucose homeostasis upon diet-induced obesity due to enhanced insulin resistance, increased inflammation and reduced generation of a subset of anti-inflammatory macrophages that are generally associated with tissue surveillance and repair.
These results suggest that IL-6 can have pro- or anti-inflammatory effects, depending on the cell or tissue context. Further investigations into the role of IL-6 signaling in macrophages in other conditions where such macrophages are important - for example, carcinogenesis or wound healing - are thus warranted.