Importantly, our data revealed that RIP1 kinase signaling to Akt is a general feature of necroptotic signaling that is observed in multiple cell types. At the same time, the significance of this connection varies in a cell type specific fashion. Importantly, in mouse lung fibroblasts, FADD-deficient Jurkat cells, and macrophages, Akt signaling contributed more prominently to an increase in TNFα synthesis, rather than cell death per se, unlike its role in L929 cells. A recent study [15] has demonstrated that, in addition to its role in necroptosis, RIP1 plays an important role in mediating the production of TNFα. These data emphasize the emerging complexity of necroptotic signaling mechanisms and highlight the major contribution of Akt to increased inflammatory signaling, specifically accompanying this form of regulated necrosis [5], [6], [10].