No association between IL‐10 promoter gene polymorphism and heart failure or rejection following cardiac transplantation

Abstract

Expression of interleukin (IL)-10 influences the frequency of rejection events after organ transplantation. Therefore, 70 heart transplant patients were genotyped for three single nucleotide polymorphisms and a microsatellite polymorphism in the promotor region of the IL-10 gene. The promoter region was amplified by polymerase chain reaction and genotyped by a colorometric oligo ligation assay and gene scan analysis, respectively. Patient groups consisted of patients suffering from dilated cardiomyopathy or ischaemic heart disease. Cardiac donors served as control group. No correlation was found between genotypes and heart failure or rejection after heart transplantation. This may indicate that in heart transplantation, the total balance of cytokine production is more important for post-transplant rejection activities than the levels of IL-10 as such.

Novel Immunosuppression: R348, a JAK3- and Syk-Inhibitor Attenuates Acute Cardiac Allograft Rejection

“…The relevance of the considerably strong suppression of IL-10 by R348, which was not observed with rapamycin, remains doubtful. IL-10 gene expression was found not to be different in human endomyocardial biopsies taken during rejection or immunological quiescence (29) and investigators have failed to demonstrate an association between IL-10 genotypes and heart transplant rejection (30). Although some groups could show that local expression of viral IL-10 prolongs cardiac allograft survival (31,32), others could not (33) and thus, its relevance during rejection remains controversial.…”

Cytokine gene polymorphisms and acute human liver graft rejection

“…27 In smaller cohorts of heart, kidney, and liver transplant recipients, no significant associations between IL-10 genotype and rejection were established. [35][36][37] Healthy individuals with the IL-10-1082-GG genotype or IL-10-592/-819/-1082 haplotype in which the IL-10-1082 component was of the IL-10-1082-GG genotype showed the greatest IL-10 production after in vitro stimulation, whereas IL-10-1082-GA and -AA showed intermediate and low production, respectively. 38,39 Conceptually, IL-10 has been termed a T H 2type cytokine because of its ability to downregulate T H 1-type cytokines and its involvement in allograft tolerance in mainly animal models.…”

The role of cytokine polymorphisms in rejection after solid organ transplantation

“…The IL-10 −1082 polymorphism has also been widely studied. Again, this SNP has not been independently associated with acute rejection 16,[18][19][20][21][22]24,25 with the exception of one small study of pediatric heart transplant recipients. 23 Nonetheless, considerable attention has focused on the effect of the combinations of IL-10 and TNF genotypes: in the initial study of cytokine polymorphisms in transplant recipients, a post-hoc analysis showed that individuals who carried both a TNF −308a allele (termed in some studies the 'high producing' allele) and the IL-10 genotype −1082a/a (the 'low producing' genotype) were at high risk of repeated acute rejection in the first 3 months after cardiac transplantation.…”