The interleukin-6 ^-174promoter polymorphism is associated with long-term kidney allograft survival

Background. Th1-dependent effector mechanisms may be responsible for allograft rejection. Recently, interleukin-6 (IL-6) has been shown to antagonize CD4⁺ T cells to effector Th2 cells and, in the process, differentiate them into Th1 cells. Methods. To assess the role of IL-6 in long-term allograft survival, 158 patients after first cadaveric kidney transplantation were analyzed for the biallelic ^-174G→C promoter polymorphism of the IL-6 gene. Results. Carriers of the ^-174C-allele (genotype GC/CC) had an inferior three-year graft survival (71/104 = 68.3%; P = 0.0059) with a 3.7-fold increased relative risk of graft loss compared to carriers of the ^-174GG-genotype (48/54 = 88.9%). The ^-174GC/CC-genotype retained its negative impact on graft survival when other established prognostic factors and further cytokine polymorphisms (^-308TNF-α, TGF-β1 codon 10 & 25, ^{-592/-819/-1082}IL-10 and ⁺⁸⁷⁴IFN-γ) were considered simultaneously. Conclusions. Since the clinical impact on transplant outcome seems as important as matching for histocompatibility antigens, genotyping of the IL-6 ^-174polymorphism may offer a new method for identifying patients at increased risk of allograft loss.