Journal Article

Analysis of Phosphodiesterase-5 (PDE5) Inhibitors in Modulating Inflammatory Markers in Humans: A Systematic Review and Meta-Analysis

Tucci, Joseph, Irving, Helen, Cianciarulo, Cassandra, Standen, Nick, Zacharias, Anita, Nguyen, Trang H.

2025

Overview

Phosphodiesterase type 5 (PDE5) inhibitors, including sildenafil, tadalafil, and vardenafil, are primarily prescribed for erectile dysfunction and pulmonary hypertension. Emerging evidence suggests they may also modulate inflammatory pathways and improve vascular function, but their effects on inflammatory biomarkers in humans remain incompletely defined. A systematic review and meta-analysis were conducted to evaluate the impact of PDE5 inhibitors on inflammatory and endothelial markers in adult humans. Randomized controlled trials comparing PDE5 inhibition to placebo were identified through electronic database searches. Outcomes included pro-inflammatory markers (TNF-α, IL-6, IL-8, CRP, VCAM-1, ICAM-1, P-selectin) and anti-inflammatory or signalling markers (IL-10, NO, cGMP), assessed at short-term (≤1 week), intermediate-term (4–6 weeks), or long-term (≥12 weeks) follow-up. Risk of bias was assessed using the Cochrane RoB 2 tool. A total of 20 studies comprising 1549 participants were included. Meta-analyses showed no significant short-term effects of PDE5 inhibition on TNF-α, IL-6, or CRP. Long-term treatment was associated with reduced IL-6 (SMD = −0.64, p = 0.002) and P-selectin (SMD = −0.57, p = 0.02), and increased cGMP (SMD = 0.87, p = 0.0003). Effects on IL-10 and nitric oxide were inconsistent across studies. Most trials had low risk of bias. PDE5 inhibitors may exert anti-inflammatory effects in long-term use by reducing vascular inflammation and enhancing cGMP signalling. These findings support further investigation of PDE5 in chronic inflammatory conditions.

• Publisher: MDPI AG,MDPI
• Subject: Bias / Biomarkers / Biomarkers - metabolism / Chronic illnesses / Clinical trials / Cytokines / Diabetes / Humans / Hypertension / Inflammation / Inflammation - drug therapy / Inflammation - metabolism / Inflammatory diseases / Insulin resistance / Intervention / Kidney diseases / Kinases / Leukocytes / Male / Meta-analysis / Metabolic syndrome / Oxidative stress / Phosphodiesterase 5 Inhibitors - pharmacology / Phosphodiesterase 5 Inhibitors - therapeutic use / Review / Systematic review / Tumor necrosis factor-TNF / Vein & artery diseases