Sildenafil Can Affect Innate and Adaptive Immune System in Both Experimental Animals and Patients

Abstract

Sildenafil, a type 5 phosphodiesterase inhibitor (PDE5-I), is primarily used for treating erectile dysfunction. Sildenafil inhibits the degradation of cyclic guanosine monophosphate (cGMP) by competing with cGMP for binding site of PDE5. cGMP is a secondary messenger activating protein kinases and a common regulator of ion channel conductance, glycogenolysis, and cellular apoptosis. PDE5 inhibitors (PDE-Is) found application in cardiology, nephrology, urology, dermatology, oncology, and gynecology. Positive result of sildenafil treatment is closely connected with its immunomodulatory effects. Sildenafil influences angiogenesis, platelet activation, proliferation of regulatory T cells, and production of proinflammatory cytokines and autoantibodies. Sildenafil action in humans and animals appears to be different. Surprisingly, it also acts differently in males and females organisms. Although the immunomodulatory effects of PDE5 inhibitors appear to be promising, none of them reached the point of being tested in clinical trials. Data on the influence of selective PDE5-Is on the human immune system are limited. The main objective of this review is to discuss the immunomodulatory effects of sildenafil in both patients and experimental animals. This is the first review of the current state of knowledge about the effects of sildenafil on the immune system.

Sildenafil Citrate Influences Production of TNF-α in Healthy Men Lymphocytes

“…Moreover, patients treated with TNF alpha inhibitors are more likely to develop infectious diseases [19,20]. Result of current experiment corresponds to our previous findings of downregulating NK cells activity by SC [8]. Kaleta and Boguska reported that SC did not influence T cell 3 Journal of Immunology Research proliferation and had no cytotoxic effect on T cells which is in line with our observations [21].…”

“…The ability of sildenafil to induce vascular smooth muscle relaxation and vasodilatation is widely utilized in the treatment of pulmonary hypertension and erectile dysfunction [5,8]. Few studies have focused on the potential usage of this drug in oncology and immunology.…”

The Effects of Administrated Sildenafil Citrate on Uterine Luminal Epithelium Height Associated with Ovarian Angiogenesis: An Experimental Animal Study

“…Sildenafil citrate (SC) or Viagra is a selective phosphodiesterase type-5 (PDE-5) inhibitor that induces vasodilation by inhibition of the cyclic guanosine monophosphate hydrolysis and increases the accessibility of the nitric oxide (NO). [ 19 20 ] For the first time, SC developed as an antihypertensive drug, and it was noted during early trials of the drug that PDE-5 inhibition led to an increased response in subjects with erectile dysfunction. [ 21 ] In recent years, many studies were performed for investigating the effects of SC on female fertility, for example, some studies indicated the positive role of vaginal SC administration on improved endometrial development.…”

Efficacy and safety of PDE5 inhibitors in the treatment of diabetes mellitus erectile dysfunction: a systematic review and meta-analysis

“…ED is one of its common chronic complications and is easily overlooked when assessing DM conditions. [27] [30] This study retrieved RCTs from various PDE5 inhibitors for the treatment of DMED and systematically evaluated their efficacy and safety. This systematic review updated one RCT study, revised the data entry problem, and added new observation indexes such as sexual satisfaction evaluation and sexual self-confidence evaluation.…”