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

Summary 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.