TNF-alpha, IL-6, IFN-gamma, and IL-10 gene expression polymorphisms and the IL-4 receptor alpha-chain variant Q576R: Effects on renal allograft outcome

Background. There has been much interest recently in the effects of various cytokine gene expression polymorphisms on graft outcome. However, the resu lts of these investigations reveal the outcomes to be organ. specific and c enter-specific. We sought to confirm and add to some of the earlier finding s by studying the impact of tumor necrosis factor-alpha (TNF-alpha), interl eukin-10 (IL-10), interferon-gamma (IFN-gamma), and interleukin-6 (IL-6) po lymorphisms and the interleukin-4 (IL-4) receptor alpha -chain variant on p osttransplant renal allograft outcome. Method. TNF-alpha, IL-6, IFN-gamma, and IL-10 gene promoter region polymorp hisms were assayed genotypically by PCR-SSP on 120 patients transplanted at the Albany Medical Center. These patients were also typed for the IL-4 rec eptor alpha -chain variant Q576R. Results. Producers of high levels of the proinflam-matory cytokine TNF-alph a were found to be at increased risk for acute rejection episodes if the al lograft was mismatched for the molecular products of the class II region of the human major histocompatibility complex (HLA-DR). Expression level poly morphisms of the IL-6, IFN-gamma, and IL-10 genes were not associated with acute rejection episodes, nor was the IL-4 receptor alpha -chain variant Q5 76R. Conclusions. These data would suggest that the production of high levels of the cytokine TNF-alpha is especially detrimental to graft survival when th e recipient's T-helper lymphocytes are being activated by mismatched donor HLA-class II antigens. Typing all potential kidney recipients for TNF-alpha , and providing well-matched organs for high producers of this cytokines, m ay be expected to increase rejection-free graft survival in these patients.