Sildenafil does not affect the proliferation of human lymphocytes in the in vitro transplant model

Abstract

Sildenafil is a selective inhibitor of type 5 phosphodiesterase (PDE5) used in the treatment of erectile dysfunction (ED) and pulmonary arterial hypertension (PAH). Numerous studies revealed beneficial effects of sildenafil use in chronic kidney disease, and also in renal, liver, heart and bone marrow transplant recipients. Some reports suggest that sildenafil modulates function of the immune system, and additionally proliferation of endothelial, bone marrow and cancer cells. Despite the fact that PDE5 inhibitors showed efficacy and safety, it is very important to know whether these drugs have immunomodulatory properties, because are used in patients after organ transplantation. The influence of sildenafil on antigen-induced proliferation of lymphocytes remains currently unknown, thus the aim of the study was to investigate the effects of the drug on human peripheral blood mononuclear cells (PBMCs) proliferation in a mixed lymphocyte reaction (MLR).PBMCs were isolated from venous blood from 30 donors. The proliferation was examined on the DNA synthesis level by measurements of 3H-thymidine incorporation. Cell viability was determined using trypan blue exclusion method.The study demonstated that sildenafil at concentrations of 0.06 µM, 0.6 µM and 6µM did not affect auto- and alloantigen-induced  proliferation of PBMCs and showed no cytotoxic effect. However, further analysis is required to fully understand the role of PDE5 inhibitors in the regulation of human immune system.