The impact of interleukin-6 promoter -597/-572/-174genotype on interleukin-6 production after lipopolysaccharide stimulation.

Interleukin (IL)-6 is a pleiotropic cytokine, produced by different cells. There is accumulating evidence that IL-6 promoter polymorphisms impact substantially on various diseases and we identified kidney transplant recipients carrying the IL-6 GGG/GGG (-597/-572/-174)genotype to have superior graft survival. To prove a functional impact on gene expression, we analysed systematically IL-6 production in healthy individuals with respect to the IL-6 (-597/-572/-174)genotype. IL-6 was determined in 100 healthy blood donors at protein and mRNA levels upon specific stimulation in monocytes and T lymphocytes under whole blood conditions. GGG/GGG individuals showed a lower IL-6 secretion upon lipopolysaccharide (LPS)-stimulation versus all others (P = 0.039). This link was even stronger when (-597) and (-174)GG genotypes were reanalysed separately (P = 0.008, P = 0.017). However, we found neither a difference at the mRNA level or percentage of CD14(+) cells nor after T cell stimulation. We found evidence for the IL-6 (-597/-572/-174)genotype to affect IL-6 synthesis, i.e. lower levels of IL-6 protein upon LPS-stimulation in GGG/GGG individuals. Further studies are needed in kidney transplant recipients to investigate the potential link between the GGG/GGG genotype and graft survival. In line with this, determination of the genetic risk profiles might be promising to improve the transplant outcome in the individual patient.