SILDENAFIL UPREGULATES TUMOR NECROSIS FACTOR α PRODUCTION IN PERIPHERAL BLOOD MONONUCLEAR CELLS OF HEALTHY MEN - PRELIMINARY REPORT
Beata Kaleta, Agnieszka Boguska, Jan Borysowski, Andrzej Górski
Abstract
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Beata Kaleta, Agnieszka Boguska, Jan Borysowski, Andrzej Górski
Abstract
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Sildenafil is a selective type 5 phosphodiesterase (PDE5) inhibitor, commonly used in the treatment of erectile dysfunction (ED) and pulmonary arterial hypertension (PAH).The results of recent studies suggest that this drug modulates function of the immune system.However, only few studies were performed in humans.Therefore, the aim of this study was to investigate the ability of sildenafil to regulate the production of proinflammatory cytokines including tumor necrosis factor alpha (TNF-α), interleukin (IL)-1β and IL-6 in peripheral blood mononuclear cells (PBMCs) from healthy men.Phorbol myristate acetate (PMA) ñ stimulated and unstimulated PBMCs from 16 participants were cultured in the absence or presence of sildenafil (400 ng/mL and 4 µg/mL).TNF-α, IL-1β and IL-6 concentrations in culture supernatants were measured by enzyme-linked immunosorbent assay (ELISA).Cell viability was assessed by trypan blue staining.Sildenafil at a concentration of 400 ng/mL significantly increased TNF-α production in stimulated PBMCs (p < 0.05) but had no effects on IL-1β and IL-6.The drug did not affect PBMCs viability.This is the first report describing such effects of sildenafil in humans.
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Sildenafil is a selective type 5 phosphodiesterase (PDE5) inhibitor, commonly used in the treatment of erectile dysfunction (ED) and pulmonary arterial hypertension (PAH).The results of recent studies suggest that this drug modulates function of the immune system.However, only few studies were performed in humans.Therefore, the aim of this study was to investigate the ability of sildenafil to regulate the production of proinflammatory cytokines including tumor necrosis factor alpha (TNF-α), interleukin (IL)-1β and IL-6 in peripheral blood mononuclear cells (PBMCs) from healthy men.Phorbol myristate acetate (PMA) ñ stimulated and unstimulated PBMCs from 16 participants were cultured in the absence or presence of sildenafil (400 ng/mL and 4 µg/mL).TNF-α, IL-1β and IL-6 concentrations in culture supernatants were measured by enzyme-linked immunosorbent assay (ELISA).Cell viability was assessed by trypan blue staining.Sildenafil at a concentration of 400 ng/mL significantly increased TNF-α production in stimulated PBMCs (p < 0.05) but had no effects on IL-1β and IL-6.The drug did not affect PBMCs viability.This is the first report describing such effects of sildenafil in humans.
Key concepts: Peripheral blood mononuclear cell, Tumor necrosis factor alpha, Sildenafil, Proinflammatory cytokine, Medicine, Endocrinology, Pharmacology, Viability assay