Cytokines and chemokine gene expression in human kidney transplantation

Abstract

Despite advances in immunosuppression in past decades, allograft rejection remains the main reason for kidney graft failure. Recently, despite great improvements in understanding of molecular basis of allograft rejections, renal histology remains the primary method to monitor the onset of graft rejection. The aim of the present study was to ascertain whether cytokine and chemokine expression profiles in kidney allografts contributed to the diagnosis of graft dysfunction. We analyzed mRNA expression in 174 kidney graft biopsies for the following cytokines: TGF-beta1, TNF-alpha, IL-10, and chemokine RANTES. Based on the expression levels obtained by real-time RT-PCR, we correlated data with the results of morphologic examinations. All tested cytokines and chemokines were upregulated (P < .001) during acute rejection compared to nonrejecting controls. Upregulation was also found in chronic allograft nephropathy (CAN) group for TGF-beta1, IL-10 (P < .001), TNF-alpha, and RANTES (P < .01). Upregulated expression of IL-10 (P < .001), TGF-beta1, (P < .01) and RANTES (P < .05) showed borderline changes. Higher expression levels (P < .001) of TGF-beta1 and IL-10 were also found during ATN. IL-10 was upregulated (P < .01) in specimens with recurrent glomerulonephritis. Weakly increased (P < .05) expressions of TGF-beta1 were found during CsA toxicity. Distinctive expression levels between acute rejection and CAN were only found for IL-10 (P < .01). TNF-alpha showed a different expression profile in acute rejection versus ATN (P < .001). These findings suggest that distinct cytokine and chemokine expression profiles in grafts may contribute to the diagnosis for and elucidation of the immunopathologic process during graft dysfunction.