Aims: 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.
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-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.