In contrast to the pro-inflammatory role of IL-6 cis-signaling in direct interaction with CD4+ T cells in TH1 immune responses and during the development of TH17 cells, IL-6 can also act in an anti-inflammatory fashion through the mIL-6Rα on macrophages because IL-6 cis-signaling inhibits the release of pro-inflammatory cytokines such as IL-12 and IL-23 by activated macrophages in vitro [82,83] and is able to promote alternative macrophage activation during obesity-related inflammation in mice leading to an ameliorated disease outcome [84]. Here, IL6 is linked to obesity due to melanocortin 4 receptor deficiency.