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-alpha, TGF-beta1 codon 10 & 25, -592/-819/-1082IL-10 and +874IFN-gamma) 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.
Müller-Steinhardt
Michael
M
Institute of Immunology and Transfusion Medicine and Department of Transplantation Medicine, University of Lübeck School of Medicine, Lübeck, Germany. mueller-steinhardt@immu.mu-luebeck.de
Härtel
Christoph
C
Müller
Brigitte
B
Kirchner
Holger
H
Fricke
Lutz
L
D005260:Female; D006085:Graft Survival / Q000235:genetics*; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D007676:Kidney Failure, Chronic / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D016030:Kidney Transplantation; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics; D012307:Risk Factors; D015996:Survival Rate; D014184:Transplantation, Homologous; D044465:White People
D015850:Interleukin-6