Different profile of gene expression of cytokines in peripheral blood mononuclear cells of transplant recipients treated with m-TOR inhibitor and calcineurin inhibitor.
OBJECTIVE
To determine how sirolimus (SRL), in comparison to calcineurin inhibitors (CNI), influences gene expression of cytokines: interleukin 1beta, tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma), and interleukin 10 (IL-10) in peripheral blood mononuclear cells (PBMC) of transplant recipients.


METHODS
Twenty-two patients (13 kidney and 9 liver transplant recipients), in which: CNI was replaced by SRL (n=11); SRL was added to CNI (n=7); or SRL was replaced by CNI (n=4), were recruited. PBMC were obtained before and after modification of immunosuppression. Real-time polymerase chain reaction was used for quantitative assessment of expression of investigated genes.


RESULTS
During therapy with SRL either with, or without CNI (SRL+/-CNI), the pro-inflammatory genes expression was increased, and IL-10 gene expression was decreased, in comparison to treatment with CNI. In subgroup of patients with malignancy as the reason of liver transplantation, gene expression of TNF-alpha and IFN-gamma was higher when SRL+/-CNI was used in comparison to treatment with CNI. Patients with viral infection receiving SRL+/-CNI had higher expression of pro-inflammatory genes than during therapy with CNI.


CONCLUSIONS
Transplant recipients during therapy with SRL+/-CNI have increased gene expression of Th1 cytokines, and decreased gene expression of Th2 cytokine, IL-10, in PBMC, compared to treatment with CNI. Our data may influence management of transplant recipients.
Department of Immunology, Transplantation Institute, Medical University of Warsaw, Nowogrodzka 59, 02-006 Warsaw, Poland. mariuszniemczyk@wp.pl
Mariusz
M
Niemczyk
Jolanta
J
Zegarska
Monika
M
Pawłowska
Janusz
J
Wyzgał
Michał
M
Ciszek
Leszek
L
Paczek
D016022:Case-Control Studies; D016572:Cyclosporine / Q000494:pharmacology / Q000627:therapeutic use*; D016207:Cytokines / Q000235:genetics*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000187:drug effects*; D016031:Liver Transplantation / Q000276:immunology; D020123:Sirolimus / Q000494:pharmacology / Q000627:therapeutic use*; D016559:Tacrolimus / Q000494:pharmacology / Q000627:therapeutic use*; D014180:Transplantation
D016207:Cytokines; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D020123:Sirolimus; D016559:Tacrolimus