Jan Mauer 1 , 2 , 3 , Bhagirath Chaurasia 1 , Julia Goldau 1 , Merly C. Vogt 1 , 2 , 3 , Johan Ruud 1 , 2 , 3 , Khoa D. Nguyen 4 , Sebastian Theurich 1 , 2 , 3 , A. Christine Hausen 1 , 2 , 3 , Joel Schmitz 1 , 5 , 6 , Hella S. Brönneke 2 , 3 , Emma Estevez 7 , Tamara L. Allen 7 , Andrea Mesaros 8 , Linda Partridge 8 , Mark A. Febbraio 7 , Ajay Chawla 4 , F. Thomas Wunderlich 1 , 2 , 3 , Jens C. Brüning 1 , 2 , 3 , 5 , 6
30 March 2014
Obesity and insulin resistance 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 show that mice with inactivated Il6ra gene in myeloid cells ( Il6ra Δmyel) displayed exaggerated deterioration of glucose homeostasis upon diet-induced obesity due to enhanced insulin resistance. Insulin target tissues showed increased inflammation and a shift in macrophage polarization. IL-6 induced IL-4-receptor expression and augmented the response to IL-4 in macrophages in a cell-autonomous manner. Il6ra Δmyel mice were resistant to IL-4-mediated alternative macrophage polarization and exhibited increased susceptibility to LPS-induced endotoxemia. These results reveal IL-6 signaling as an important determinant for alternative macrophage-activation and assign IL-6 an unexpected homeostatic role to limit inflammation.