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PDE5 inhibitors blunt inflammation in human BPH: A potential mechanism of action for PDE5 inhibitors in LUTS
Author(s) -
Vignozzi Linda,
Gacci Mauro,
Cellai Ilaria,
Morelli Annamaria,
Maneschi Elena,
Comeglio Paolo,
Santi Raffaella,
Filippi Sandra,
Sebastianelli Arcangelo,
Nesi Gabriella,
Serni Sergio,
Carini Marco,
Maggi Mario
Publication year - 2013
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.22686
Subject(s) - blunt , inflammation , mechanism of action , medicine , mechanism (biology) , action (physics) , pharmacology , chemistry , surgery , biochemistry , physics , in vitro , quantum mechanics
BACKGROUND Metabolic syndrome (MetS) and benign prostate hyperplasia (BPH)/low urinary tract symptoms (LUTS) are often comorbid. Chronic inflammation is one of the putative links between these diseases. Phosphodiesterase type 5 inhibitors (PDE5i) are recognized as an effective treatment of BPH‐related LUTS. One proposed mechanism of action of PDE5 is the inhibition of intraprostatic inflammation. In this study we investigate whether PDE5i could blunt inflammation in the human prostate. METHODS Evaluation of the effect of tadalafil and vardenafil on secretion of interleukin 8 (IL‐8, a surrogate marker of prostate inflammation) by human myofibroblast prostatic cells (hBPH) exposed to different inflammatory stimuli. We preliminary evaluate histological features of prostatic inflammatory infiltrates in BPH patients enrolled in a randomized, double bind, placebo controlled study aimed at investigating the efficacy of vardenafil (10 mg/day, for 12 weeks) on BPH/LUTS. RESULTS In vitro treatment with tadalafil or vardenafil on hBPH reduced IL‐8 secretion induced by either TNFα or metabolic factors, including oxidized low‐density lipoprotein, oxLDL, to the same extent as a PDE5‐insensitive PKG agonist Sp‐8‐Br‐PET‐cGMP. These effects were reverted by the PKG inhibitor KT5823, suggesting a cGMP/PKG‐dependency. Treatment with tadalafil or vardenafil significantly suppressed oxLDL receptor (LOX‐1) expression. Histological evaluation of anti‐CD45 staining (CD45 score) in prostatectomy specimens of BPH patients showed a positive association with MetS severity. Reduced HDL‐cholesterol and elevated triglycerides were the only MetS factors significantly associated with CD45 score. In the MetS cohort there was a significant lower CD45 score in the vardenafil‐arm versus the placebo‐one. Prostate 73: 1391–1402, 2013 . © 2013 Wiley Periodicals, Inc.