| First Author | Mauer J | Year | 2014 |
| Journal | Nat Immunol | Volume | 15 |
| Issue | 5 | Pages | 423-30 |
| PubMed ID | 24681566 | Mgi Jnum | J:209976 |
| Mgi Id | MGI:5569195 | Doi | 10.1038/ni.2865 |
| Citation | Mauer J, et al. (2014) Signaling by IL-6 promotes alternative activation of macrophages to limit endotoxemia and obesity-associated resistance to insulin. Nat Immunol 15(5):423-30 |
| abstractText | Obesity and resistance to insulin are closely associated with the development of low-grade inflammation. Interleukin 6 (IL-6) is linked to obesity-associated inflammation; however, its role in this context remains controversial. Here we found that mice with an inactivated gene encoding the IL-6Ralpha chain of the receptor for IL-6 in myeloid cells (Il6ra(Deltamyel) mice) developed exaggerated deterioration of glucose homeostasis during diet-induced obesity, due to enhanced resistance to insulin. Tissues targeted by insulin showed increased inflammation and a shift in macrophage polarization. IL-6 induced expression of the receptor for IL-4 and augmented the response to IL-4 in macrophages in a cell-autonomous manner. Il6ra(Deltamyel) mice were resistant to IL-4-mediated alternative polarization of macrophages and exhibited enhanced susceptibility to lipopolysaccharide (LPS)-induced endotoxemia. Our results identify signaling via IL-6 as an important determinant of the alternative activation of macrophages and assign an unexpected homeostatic role to IL-6 in limiting inflammation. |
