Advertisement

Current Urology Reports

, 15:463 | Cite as

The Role of Inflammation in Lower Urinary Tract Symptoms (LUTS) due to Benign Prostatic Hyperplasia (BPH) and Its Potential Impact on Medical Therapy

  • Vincenzo FicarraEmail author
  • Marta Rossanese
  • Michele Zazzara
  • Gianluca Giannarini
  • Maria Abbinante
  • Riccardo Bartoletti
  • Vincenzo Mirone
  • Francesco Scaglione
Benign Prostatic Hyperplasia (K McVary, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Benign Prostatic Hyperplasia

Abstract

A chronic prostatic inflammation seems to play a crucial role in benign prostatic hyperplasia (BPH) pathogenesis and progression. Therefore, inflammation could represent a new potential target for medical therapy of lower urinary tract symptoms (LUTS) due to BPH (LUTS/BPH). This review article analyzes the evidence supporting the role of inflammation in the onset and progression of BPH, and it assesses the potential impact of previous mechanisms on medical therapy of LUTS/BPH. Literature data support the role of inflammation as a relevant factor in the pathogenesis of BPH. Indeed, several data favour the role of infiltrating lymphocytes in the development and progression of prostate adenoma as an effect of a self-maintaining remodeling process. Although available drugs commonly used in the treatment of LUTS/BPH do not exhibit an anti-inflammatory activity, it seems to be obvious considering the inflammation as a new target in the treatment of LUTS/BPH. Drugs currently investigated for the treatment of prostatic inflammation include the hexanic lipidosterolic extract of Serenoa repens, nonsteroidal anti-inflammatory drugs, and vitamin D receptor agonists.

Keywords

Inflammation Lower urinary tract symptoms Benign prostatic hyperplasia Medical therapy 

Notes

Compliance with Ethics Guidelines

Conflict of Interest

Prof. Vincenzo Ficarra reports a grant and personal fees from Pierre Fabre.

Prof. Riccardo Bartoletti reports a grant and personal fees from Takeda Company and Pierre Fabre.

Dr. Marta Rossanese, Dr. Michele Zazzara, Dr. Gianluca Giannarini, Dr. Maria Abbinante, Prof. Vincenzo Mirone, and Dr. Francesco Scaglione each declare no potential conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Ribal MJ. The link between benign prostatic hyperplasia and inflammation. Eur Urol Suppl. 2013;12:103–9.CrossRefGoogle Scholar
  2. 2.
    Sampson N, Untergasser G, Plas E, Berger P. The ageing male reproductive tract. J Pathol. 2007;211:206–18.PubMedCrossRefGoogle Scholar
  3. 3.
    Nickel JC, Roehrborn CG, O’Leary MP, Bostwick DG, Somerville MC, Rittmaster RS. The relationship between prostate inflammation and lower urinary tract symptoms: examination of baseline data from the REDUCE trial. Eur Urol. 2008;54:1379–84.PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.•
    De Nunzio C, Kramer G, Marberger M, et al. The controversial relationship between benign prostatic hyperplasia and prostate cancer: the role of inflammation. Eur Urol. 2011;60:106–17. This is a very comprehensive review article investigating the relationship between inflammation and benign prostatic hyperplasia. The article suggested that chronic prostatic inflammation may be involved in the development and progression of chronic prostatic disease, although there is still no evidence of a causal relation. Inflammation should be considered a new domain in basic and clinical research in patients with BPH.PubMedCrossRefGoogle Scholar
  5. 5.
    Steiner GE, Newman ME, Paikl D, et al. Expression and function of proinflammatory interleukin IL-17 and IL-17 receptor in normal, benign hyperplastic, and malignant prostate. Prostate. 2003;56:171–82.PubMedCrossRefGoogle Scholar
  6. 6.
    Steiner GE, Stix U, Handisurya A, et al. Cytokine expression pattern in benign prostatic hyperplasia infiltrating T cells and impact of lymphocytic infiltration on cytokine mRNA profile in prostatic tissue. Lab Invest. 2003;83:1131–46.PubMedCrossRefGoogle Scholar
  7. 7.•
    Ficarra V, Sekulovic S, Zattoni F, Zazzara M, Novara G. Why and how to evaluate chronic prostatic inflammation. Eur Urol Suppl. 2013;12:110–5. This review describes the recent literature regarding the relationship between prostatic inflammation and BPH and focuses on the clinical perspective of why and how to evaluate prostatic inflammation. The article highlighted the potential role of biomarkers, prostatic calcifications, symptoms severity, and metabolic syndrome to identify clinically patients with suspicious prostatic inflammation.CrossRefGoogle Scholar
  8. 8.
    Ficarra V. Is chronic prostatic inflammation a new target in the medical therapy of lower urinary tract symptoms (LUTS) due to benign prostate hyperplasia (BPH)? BJU Int. 2013;112:421–2.PubMedCrossRefGoogle Scholar
  9. 9.••
    Gandaglia G, Briganti A, Gontero P, et al. The role of chronic prostatic inflammation in the pathogenesis and progression of benign prostatic hyperplasia (BPH). BJU Int. 2013;112:432–41. In this review article, the authors highlighted that although the histological examination of prostatic tissue remains the only available method to diagnose chronic inflammation, different parameters, such as prostatic calcifications, prostate volume, LUTS severity, storage and prostatitis-like symptoms, poor response to medical therapies, and urinary biomarkers, have been shown to be correlated with chronic inflammation.PubMedCrossRefGoogle Scholar
  10. 10.
    Robert G, Descazeaud A, Allory Y, Vacherot F, de la Taille A. Should we investigate prostatic inflammation for the management of benign prostatic hyperplasia? Eur Urol Suppl. 2009;8:879–86.CrossRefGoogle Scholar
  11. 11.
    De Nunzio C, Aronson W, Freedland SJ, Giovannucci E, Parsons JK. The correlation between metabolic syndrome and prostatic diseases. Eur Urol. 2012;61:560–70.PubMedCrossRefGoogle Scholar
  12. 12.
    Oelke M, Bachmann A, Descazeaud A, et al. Guidelines on the management of male lower urinary tract symptoms (LUTS), incl. benign prostatic obstruction (BPO). Eur Assoc Urol. Web site http://www.uroweb.org.
  13. 13.
    Fullhase C, Chapple C, Cornu JN, et al. Systematic review of combination drug therapy for nonneurogenic male lower urinary tract symptoms. Eur Urol. 2013;64:228–43.PubMedCrossRefGoogle Scholar
  14. 14.
    Madersbacher S, Marszalek M, Lackner J, et al. The long-term outcome of medical therapy for BPH. Eur Urol. 2007;51:1522–33.PubMedCrossRefGoogle Scholar
  15. 15.
    Christ GJ, Andersson KE. Rho-kinase and effects of Rho-kinase inhibition on the lower urinary tract. Neurourol Urodyn. 2007;26:948–54.PubMedCrossRefGoogle Scholar
  16. 16.
    Hennenberg M, Stief CG, Gratzke C. Prostatic α1-adrenoceptors: new concepts of function, regulation, and intracellular signaling. Neurourol Urodyn. 2014;33(7):1074–85.PubMedGoogle Scholar
  17. 17.••
    Kwon YK, Choe MS, Seo KW, et al. The effect of intraprostatic chronic inflammation on benign prostatic hyperplasia treatment. Korean J Urol. 2010;51:266–70. This prospective clinical study showed that in patients with high-grade prostatic inflammation the use of alpha-blockers combined with 5-alpha-reductase inhibitors can be insufficient to reduce symptom severity, thus highlighting the need for alternative drugs. Google Scholar
  18. 18.••
    de la Taille A. Therapeutic approach: the importance of controlling prostatic inflammation. Eur Urol Suppl. 2013;12:116–23. This review article examined the evidence for the role of inflammation in BPH and the use of various drug classes to reduce and prevent prostatic inflammation, with a particular focus on hexanic lipidosterolic extract of Serenoa repens (Permixon). Scientific evidence supports the conclusion that hexanic extract of Serenoa repens treats BPH through several mechanisms, one of which is reduction of inflammation.CrossRefGoogle Scholar
  19. 19.
    Kahokehr A, Vather R, Nixon A, Hill AG. Non-steroidal anti-inflammatory drugs for lower urinary tract symptoms in benign prostatic hyperplasia: systematic review and meta-analysis of randomized controlled trials. BJU Int. 2013;111(2):304–11.PubMedCrossRefGoogle Scholar
  20. 20.
    Colli E, Rigatti P, Montorsi F, et al. BXL628, a novel vitamin D3 analog arrests prostate growth in patients with benign prostatic hyperplasia: a randomized clinical trial. Eur Urol. 2006;49:82–6.PubMedCrossRefGoogle Scholar
  21. 21.
    Cornu JN, Cussenot O, Haab F, Lukacs B. A widespread population study of actual medical management of lower urinary tract symptoms related to benign prostatic hyperplasia across Europe and beyond official clinical guidelines. Eur Urol. 2010;58:450–6.PubMedCrossRefGoogle Scholar
  22. 22.
    Latil A, Libon C, Templier M, Junquero D, Lantoine-Adam F, Nguyen T. Hexanic lipidosterolic extract of Serenoa repens inhibits the expression of two key inflammatory mediators, MCP-1/CCL2 and VCAM-1, in vitro. BJU Int. 2012;110:301–7.CrossRefGoogle Scholar
  23. 23.
    Vela Navarrete R, Garcia Cardoso JV, Barat A, Manzarbeitia F, López FA. BPH and inflammation: pharmacological effects of Permixon on histological and molecular inflammatory markers. Results of a double blind pilot clinical assay. Eur Urol. 2003;44:549–55.PubMedCrossRefGoogle Scholar
  24. 24.
    Exploratory study of L.S.E.S.r. (lipidosterolic extract of Serenoa repens) (PERMIXON1 160 mg hard capsule) versus tamsulosine LP activity on inflammation biomarkers in the treatment of urinary symptoms related to BPH (benign prostatic hyperplasia) (PERMIN). NCT01604811. ClinicalTrials.gov Web site. http://clinicaltrials.gov/ct2/show/NCT01604811?term=serenoa+repens&rank=4.

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Vincenzo Ficarra
    • 1
    Email author
  • Marta Rossanese
    • 2
  • Michele Zazzara
    • 2
  • Gianluca Giannarini
    • 1
  • Maria Abbinante
    • 1
  • Riccardo Bartoletti
    • 3
  • Vincenzo Mirone
    • 4
  • Francesco Scaglione
    • 5
  1. 1.Department of Experimental and Clinical Medical Sciences, Urology UnitUniversity of Udine, Academic Medical Centre Hospital UdineUdineItaly
  2. 2.Department of Surgical, Oncologic and Gastrointestinal Sciences, Urologic UnitUniversity of PadovaPaduaItaly
  3. 3.Department of UrologyUniversity of FlorenceFlorenceItaly
  4. 4.Department of UrologyUniversity of NaplesNaplesItaly
  5. 5.Department of Medical Biotechnologies and Translational MedicineUniversity of MilanMilanItaly

Personalised recommendations