title: PDE5 inhibitors blunt inflammation in human BPH: a potential mechanism of action for PDE5 inhibitors in LUTS.
abstract: 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.
authors.affiliation: Department of Experimental and Clinical Biomedical Sciences, Sexual Medicine and Andrology Unit, University of Florence, Florence, Italy.
authors.forename: Linda
authors.initials: L
authors.lastname: Vignozzi
authors.forename: Mauro
authors.initials: M
authors.lastname: Gacci
authors.forename: Ilaria
authors.initials: I
authors.lastname: Cellai
authors.forename: Annamaria
authors.initials: A
authors.lastname: Morelli
authors.forename: Elena
authors.initials: E
authors.lastname: Maneschi
authors.forename: Paolo
authors.initials: P
authors.lastname: Comeglio
authors.forename: Raffaella
authors.initials: R
authors.lastname: Santi
authors.forename: Sandra
authors.initials: S
authors.lastname: Filippi
authors.forename: Arcangelo
authors.initials: A
authors.lastname: Sebastianelli
authors.forename: Gabriella
authors.initials: G
authors.lastname: Nesi
authors.forename: Sergio
authors.initials: S
authors.lastname: Serni
authors.forename: Marco
authors.initials: M
authors.lastname: Carini
authors.forename: Mario
authors.initials: M
authors.lastname: Maggi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002243:Carbolines / Q000494:pharmacology* / Q000627:therapeutic use; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D004311:Double-Blind Method; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology* / Q000627:therapeutic use; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D016209:Interleukin-8 / Q000378:metabolism*; D059411:Lower Urinary Tract Symptoms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D058628:Myofibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D058986:Phosphodiesterase 5 Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D010865:Pilot Projects; D010879:Piperazines / Q000494:pharmacology* / Q000627:therapeutic use; D011467:Prostate / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011470:Prostatic Hyperplasia / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D013450:Sulfones / Q000494:pharmacology / Q000627:therapeutic use; D000068581:Tadalafil; D016896:Treatment Outcome; D014227:Triazines / Q000494:pharmacology / Q000627:therapeutic use; D000069058:Vardenafil Dihydrochloride
chemical_list: C104224:8-bromo-beta-phenylethenoguanosine 3',5'-cyclic monophosphate; D002243:Carbolines; D007093:Imidazoles; D016209:Interleukin-8; D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines; D013450:Sulfones; D014227:Triazines; D000069058:Vardenafil Dihydrochloride; D000068581:Tadalafil; D006152:Cyclic GMP
keywords: BPH/LUTS; PDE5 inhibitors; inflammation; lipids; metabolic syndrome; prostate; tadalafil; vardenafil