TNF-α and IFN-γ gene variation and genetic susceptibility to type 1 diabetes and its microangiopathic complications

Background TNF-α has accelerating role in development of type 1 diabetes. Although an immunosupressor function and leading protecting role in T1DM also has been claimed for this pro-inflammatory cytokine. Over-expression of pro-inflammatory and type 1 cytokines (Th1, like IFN-γ) drive insulitis toward the destructive form that leads to type 1 diabetes (T1DM). Among type 1 cytokines only IFN-γ has been detectable in the islet β cells. In deletion studies IFN-γ was also the only Th1 cytokine for which its ablation or blockade caused delayed or decreased incidence of T1DM.