Different profile of gene expression of cytokines in peripheral blood mononuclear cells of transplant recipients treated with m-TOR inhibitor and calcineurin inhibitor

Abstract

Aims To determine how sirolimus (SRL), in comparison to calcineurin inhibitors (CNI), influences gene expression of cytokines: interleukin 1β, tumor necrosis factor α (TNF-α), interferon γ (IFN-γ), and interleukin 10 (IL-10) in peripheral blood mononuclear cells (PBMC) of transplant recipients. Material and 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-α and IFN-γ 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.