Mycophenolate mofetil but not the type of calcineurin inhibitor (cyclosporine vs tacrolimus) influences the intragraft mRNA expression of cytokines in human kidney allograft biopsies by in situ RT-PCR analysis.
The aim of the study was to assess the molecular background of the alloimmune response by the detection of low-abundance mRNA of cytokines in 34 core needle biopsies from kidney allografts with histopathological findings of acute rejection (AR). Recipients were immunosuppressed with a calcineurin inhibitor (CNI), cyclosporine or tacrolimus, and prednisone and azathioprine or mycophenolate mofetil (MMF). Tubular and glomerular expression of IL-2, IL-6, IL-10, IFN-gamma, TGF-beta1, and PDGF-B mRNA were assessed using semiquantitative evaluations of RT-PCR in situ on paraffin tissue sections. This procedure resulted in light microscopy visualization of granular precipitates at the sites of the corresponding mRNA chains. The tubular expression of mRNA for IL-6 and TGF-beta1 was significantly lower in biopsies with AR (n = 34) obtained from patients treated with MMF (n = 12) than in biopsies obtained from patients treated with azathioprine (n = 22) (P < .02). Responsiveness to corticosteroids tended to be more frequent among the MMF group (11 of 12 recipients vs 15 of 22 recipients, P = ns). Moreover, 8 of 12 recipients in the MMF-treated group displayed serum creatinine levels equal or less than 167 mmol/L 1 year after biopsy compared to 7 of 22 recipients in the azathioprine-treated group. There was no significant difference between the groups that had or had not received corticosteroids or between those treated with each type of CNI. These results suggest stronger inhibition of humoral responses and down-regulation of fibrosis by MMF among recipients with AR.
Kaminska
D
D
Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Wroclaw, Poland.
Tyran
B
B
Mazanowska
O
O
Letachowicz
W
W
Kochman
A
A
Rabczynski
J
J
Szyber
P
P
Patrzalek
D
D
Chudoba
P
P
Klinger
M
M
D001706:Biopsy; D065095:Calcineurin Inhibitors; D016572:Cyclosporine / Q000627:therapeutic use*; D016207:Cytokines / Q000235:genetics*; D004359:Drug Therapy, Combination; D006133:Growth Substances / Q000235:genetics; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000276:immunology* / Q000473:pathology; D007684:Kidney Tubules / Q000276:immunology / Q000473:pathology; D019520:Living Donors; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D016559:Tacrolimus / Q000627:therapeutic use*; D014158:Transcription, Genetic / Q000276:immunology*; D014184:Transplantation, Homologous / Q000276:immunology / Q000473:pathology
D065095:Calcineurin Inhibitors; D016207:Cytokines; D006133:Growth Substances; D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D016572:Cyclosporine; D009173:Mycophenolic Acid; D016559:Tacrolimus