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Analysis of Phosphodiesterase-5 (PDE5) Inhibitors in Modulating Inflammatory Markers in Humans: A Systematic Review
Cassandra Cianciarulo1,2, Trang H Nguyen1,2, Anita Zacharias1,3
1Holsworth Biomedical Research Centre, Department of Rural Clinical Sciences, La Trobe Rural Health School, La Trobe University, Bendigo, VIC 3550, Australia.
International Journal of Molecular Sciences
|August 14, 2025
Summary
Phosphodiesterase type 5 (PDE5) inhibitors show long-term anti-inflammatory effects, reducing IL-6 and P-selectin while increasing cGMP. These findings suggest potential benefits for chronic inflammatory conditions.
Area of Science:
- Pharmacology
- Immunology
- Cardiovascular Medicine
Background:
- Phosphodiesterase type 5 (PDE5) inhibitors are established treatments for erectile dysfunction and pulmonary hypertension.
- Emerging research indicates PDE5 inhibitors may influence inflammatory pathways and vascular health.
- The precise impact of PDE5 inhibitors on human inflammatory biomarkers requires further elucidation.
Purpose of the Study:
- To systematically review and meta-analyze the effects of PDE5 inhibitors on inflammatory and endothelial markers in adult humans.
- To assess short-term, intermediate-term, and long-term impacts of PDE5 inhibition on specific biomarkers.
- To evaluate the risk of bias in relevant randomized controlled trials.
Main Methods:
- Systematic review and meta-analysis of randomized controlled trials comparing PDE5 inhibitors with placebo.
- Inclusion of studies measuring pro-inflammatory (TNF-α, IL-6, IL-8, CRP, VCAM-1, ICAM-1, P-selectin) and anti-inflammatory/signaling markers (IL-10, NO, cGMP).
- Assessment of outcomes at various follow-up durations and evaluation of study bias using the Cochrane RoB 2 tool.
Main Results:
- No significant short-term effects observed for TNF-α, IL-6, or CRP.
- Long-term PDE5 inhibition demonstrated a reduction in IL-6 and P-selectin levels.
- Long-term treatment also showed a significant increase in cyclic guanosine monophosphate (cGMP) levels.
Conclusions:
- Long-term use of PDE5 inhibitors may exert anti-inflammatory effects, particularly by reducing vascular inflammation.
- Enhanced cyclic guanosine monophosphate (cGMP) signaling is a key mechanism associated with these benefits.
- Further research into the role of PDE5 inhibitors in managing chronic inflammatory diseases is warranted.
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