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Inflammatory mechanisms associated with prostatic inflammation and lower urinary tract symptoms

  • Jennifer L. St. SauverEmail author
  • Steven J. Jacobsen
Article

Abstract

Inflammation is a common finding in histologic prostate specimens obtained from aging men. Accumulating data suggest that inflammation may play an important role in the development of benign prostatic hyperplasia (BPH), and the development and progression of lower urinary tract symptoms (LUTS). Inflammatory processes may contribute to prostatic enlargement directly through stimulation of prostate growth, or, alternatively, through decreasing prostatic apoptosis. Inflammatory processes may also impact other components of the urogenital tract, such as the bladder, and contribute to LUTS regardless of the presence of prostate enlargement. Therefore, current research offers clues about converging inflammatory pathways that may be targeted to improve treatment of BPH and/or LUTS, as well as identifying potential targets for the prevention of these syndromes.

Keywords

Benign Prostatic Hyperplasia Lower Urinary Tract Symptom Prostate Volume Acute Urinary Retention Dutasteride 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References and Recommended Reading

  1. 1.
    Berry SJ, Coffey DS, Walsh PC, Ewing LL: The development of human benign prostatic hyperplasia with age. J Urol 1984, 132:474–479.PubMedGoogle Scholar
  2. 2.
    Sarma AV, Wei JT, Jacobson DJ, et al.: Comparison of lower urinary tract symptom severity and associated bother between community-dwelling black and white men: the Olmsted County Study of Urinary Symptoms and Health Status and the Flint Men’s Health Study. Urology 2003, 61:1086–1091.PubMedCrossRefGoogle Scholar
  3. 3.
    Wei JT, Calhoun E, Jacobsen SJ: Urologic diseases in America project: benign prostatic hyperplasia. J Urol 2005, 173:1256–1261.PubMedCrossRefGoogle Scholar
  4. 4.
    Jacobsen SJ, Girman CJ, Guess HA, et al.: New diagnostic and treatment guidelines for benign prostatic hyperplasia. Potential impact in the United States. Arch Intern Med 1995, 155:477–481.PubMedCrossRefGoogle Scholar
  5. 5.
    Kohnen PW, Drach GW: Patterns of inflammation in prostatic hyperplasia: a histologic and bacteriologic study. J Urol 1979, 121:755–760.PubMedGoogle Scholar
  6. 6.
    Di Silverio F, Gentile V, De Matteis A, et al.: Distribution of inflammation, pre-malignant lesions, incidental carcinoma in histologically confirmed benign prostatic hyperplasia: a retrospective analysis. Eur Urol 2003, 43:164–175.PubMedCrossRefGoogle Scholar
  7. 7.
    Gerstenbluth RE, Seftel AD, MacLennan GT, et al.: Distribution of chronic prostatitis in radical prostatectomy specimens with up-regulation of bcl-2 in areas of inflammation. J Urol 2002, 167:2267–2270.PubMedCrossRefGoogle Scholar
  8. 8.
    Anim JT, Kehinde EO, Prasad A, et al.: Relationship between serum prostate specific antigen and the pattern of inflammation in both benign and malignant prostatic disease in Middle Eastern men. Int Urol Nephrol 2006, 38:27–32.PubMedCrossRefGoogle Scholar
  9. 9.
    Roehrborn C, Kaplan SA, Noble WD, et al.: The impact of acute or chronic inflammation in baseline biopsy on the risk of clinical progression of BPH: results of the MTOP study [abstract]. J Urol 2005, 173:204.CrossRefGoogle Scholar
  10. 10.
    Rohrmann S, De Marzo AM, Smit E, et al.: Serum C-reactive protein concentration and lower urinary tract symptoms in older men in the Third National Health and Nutrition Examination Survey (NHANES III). Prostate 2005, 62:27–33.PubMedCrossRefGoogle Scholar
  11. 11.
    Nickel JC, Roehrborn CG, O’Leary MP, et al.: Examination of the relationship between symptoms of prostatitis and histological inflammation: baseline data from the REDUCE chemoprevention trial. J Urol 2007, 178:896–900; discussion 900–891.PubMedCrossRefGoogle Scholar
  12. 12.
    Collins GN, Lee RJ, McKelvie GB, et al.: Relationship between prostate specific antigen, prostate volume and age in the benign prostate. Br J Urol 1993, 71:445–450.PubMedCrossRefGoogle Scholar
  13. 13.
    St Sauver JL, Jacobson DJ, Girman CJ, et al.: Tracking of longitudinal changes in measures of benign prostatic hyperplasia in a population based cohort. J Urol 2006, 175:1018–1022; discussion 1022.PubMedCrossRefGoogle Scholar
  14. 14.
    Tuncel A, Uzun B, Eruyar T, et al.: Do prostatic infarction, prostatic inflammation and prostate morphology play a role in acute urinary retention? Eur Urol 2005, 48:277–283; discussion 283–274.PubMedCrossRefGoogle Scholar
  15. 15.
    Kefi A, Koseoglu H, Celebi I, et al.: Relation between acute urinary retention, chronic prostatic inflammation and accompanying elevated prostate-specific antigen. Scand J Urol Nephrol 2006, 40:155–160.PubMedCrossRefGoogle Scholar
  16. 16.
    Mishra VC, Allen DJ, Nicolaou C, et al.: Does intraprostatic inflammation have a role in the pathogenesis and progression of benign prostatic hyperplasia? BJU Int 2007, 100:327–331.PubMedCrossRefGoogle Scholar
  17. 17.
    Kessler OJ, Keisari Y, Servadio C, Abramovici A: Role of chronic inflammation in the promotion of prostatic hyperplasia in rats. J Urol 1998, 159:1049–1053.PubMedCrossRefGoogle Scholar
  18. 18.
    Steiner G, Gessl A, Kramer G, et al.: Phenotype and function of peripheral and prostatic lymphocytes in patients with benign prostatic hyperplasia. J Urol 1994, 151:480–484.PubMedGoogle Scholar
  19. 19.
    Bostwick DG, de la Roza G, Dundore P, et al.: Intraepithelial and stromal lymphocytes in the normal human prostate. Prostate 2003, 55:187–193.PubMedCrossRefGoogle Scholar
  20. 20.
    Anim JT, Udo C, John B: Characterisation of inflammatory cells in benign prostatic hyperplasia. Acta Histochem 1998, 100:439–449.PubMedCrossRefGoogle Scholar
  21. 21.
    Kramer G, Mitteregger D, Marberger M: Is benign prostatic hyperplasia (BPH) an immune inflammatory disease? Eur Urol 2007, 51:1202–1216.PubMedCrossRefGoogle Scholar
  22. 22.
    Handisurya A, Steiner GE, Stix U, et al.: Differential expression of interleukin-15, a pro-inflammatory cytokine and T-cell growth factor, and its receptor in human prostate. Prostate 2001, 49:251–262.PubMedCrossRefGoogle Scholar
  23. 23.
    Kakehi Y, Segawa T, Wu XX, et al.: Down-regulation of macrophage inhibitory cytokine-1/prostate derived factor in benign prostatic hyperplasia. Prostate 2004, 59:351–356.PubMedCrossRefGoogle Scholar
  24. 24.
    Taoka R, Tsukuda F, Ishikawa M, et al.: Association of prostatic inflammation with down-regulation of macrophage inhibitory cytokine-1 gene in symptomatic benign prostatic hyperplasia. J Urol 2004, 171:2330–2335.PubMedCrossRefGoogle Scholar
  25. 25.
    Steiner GE, Newman ME, Paikl D, et al.: Expression and function of pro-inflammatory interleukin IL-17 and IL-17 receptor in normal, benign hyperplastic, and malignant prostate. Prostate 2003, 56:171–182.PubMedCrossRefGoogle Scholar
  26. 26.
    Penna G, Mondaini N, Amuchastegui S, et al.: Seminal plasma cytokines and chemokines in prostate inflammation: interleukin 8 as a predictive biomarker in chronic prostatitis/chronic pelvic pain syndrome and benign prostatic hyperplasia. Eur Urol 2007, 51:524–533; discussion 533.PubMedCrossRefGoogle Scholar
  27. 27.
    Royuela M, Ricote M, Parsons MS, et al.: Immunohistochemical analysis of the IL-6 family of cytokines and their receptors in benign, hyperplasic, and malignant human prostate. J Pathol 2004, 202:41–49.PubMedCrossRefGoogle Scholar
  28. 28.
    Kramer G, Steiner GE, Handisurya A, et al.: Increased expression of lymphocyte-derived cytokines in benign hyperplastic prostate tissue, identification of the producing cell types, and effect of differentially expressed cytokines on stromal cell proliferation. Prostate 2002, 52:43–58.PubMedCrossRefGoogle Scholar
  29. 29.
    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, 1131–1146.PubMedCrossRefGoogle Scholar
  30. 30.
    Giri D, Ittmann M: Interleukin-8 is a paracrine inducer of fibroblast growth factor 2, a stromal and epithelial growth factor in benign prostatic hyperplasia. Am J Pathol 2001, 159:139–147.PubMedCrossRefGoogle Scholar
  31. 31.
    Castro P, Xia C, Gomez L, et al.: Interleukin-8 expression is increased in senescent prostatic epithelial cells and promotes the development of benign prostatic hyperplasia. Prostate 2004, 60:153–159.PubMedCrossRefGoogle Scholar
  32. 32.
    Faour WH, Mancini A, He QW, Di Battista JA: T-cell-derived interleukin-17 regulates the level and stability of cyclooxygenase-2 (COX-2) mRNA through restricted activation of the p38 mitogen-activated protein kinase cascade: role of distal sequences in the 3′-untranslated region of COX-2 mRNA. J Biol Chem 2003, 278:26897–26907.PubMedCrossRefGoogle Scholar
  33. 33.
    Wang W, Bergh A, Damber JE: Chronic inflammation in benign prostate hyperplasia is associated with focal upregulation of cyclooxygenase-2, Bcl-2, and cell proliferation in the glandular epithelium. Prostate 2004, 61:60–72.PubMedCrossRefGoogle Scholar
  34. 34.
    Lin VK, Wang SY, Roehrborn C: Alpha adrenergic stimulation regulates cox-2 expression in prostate stroma cells (abstract). J Urol 2005, 173(Suppl):390.Google Scholar
  35. 35.
    Kyprianou N, Tu H, Jacobs SC: Apoptotic versus proliferative activities in human benign prostatic hyperplasia. Hum Pathol 1996, 27:668–675.PubMedCrossRefGoogle Scholar
  36. 36.
    Shariat SF, Ashfaq R, Roehrborn CG, et al.: Expression of survivin and apoptotic biomarkers in benign prostatic hyperplasia. J Urol 2005, 174:2046–2050.PubMedCrossRefGoogle Scholar
  37. 37.
    Rittmaster RS, Norman RW, Thomas LN, Rowden G: Evidence for atrophy and apoptosis in the prostates of men given finasteride. J Clin Endocrinol Metab 1996, 81:814–819.PubMedCrossRefGoogle Scholar
  38. 38.
    Huynh H: Induction of apoptosis in rat ventral prostate by finasteride is associated with alteration in MAP kinase pathways and Bcl-2 related family of proteins. Int J Oncol 2002, 20:1297–1303.PubMedGoogle Scholar
  39. 39.
    Tahmatzopoulos A, Kyprianou N: Apoptotic impact of alpha1-blockers on prostate cancer growth: a myth or an inviting reality? Prostate 2004, 59:91–100.PubMedCrossRefGoogle Scholar
  40. 40.
    Garrison JB, Kyprianou N: Doxazosin induces apoptosis of benign and malignant prostate cells via a death receptor-mediated pathway. Cancer Res 2006, 66:464–472.PubMedCrossRefGoogle Scholar
  41. 41.
    Roehrborn CG: Three months’ treatment with the alpha1-blocker alfuzosin does not affect total or transition zone volume of the prostate. Prostate Cancer Prostatic Dis 2006, 9:121–125.PubMedCrossRefGoogle Scholar
  42. 42.
    St. Sauver JL, Jacobson D, McGree ME, et al.: Protective association between non-steroidal anti-inflammatory drug use and measures of benign prostatic hyperplasia. Am J Epidemiol 2006, 164:760–768.PubMedCrossRefGoogle Scholar
  43. 43.
    Minnery CH, Getzenberg RH: Benign prostatic hyperplasia cell line viability and modulation of jm-27 by doxazosin and Ibuprofen. J Urol 2005, 174:375–379.PubMedCrossRefGoogle Scholar
  44. 44.
    Vela Navarrete R, Garcia Cardoso JV, Barat A, et al.: BPH and inflammation: pharmacological effects of Permixon on histological and molecular inflammatory markers. Results of a double blind pilot clinical assay. Eur Urol 2003, 44:549–555.PubMedCrossRefGoogle Scholar
  45. 45.
    Maggi CA, Evangelista S, Grimaldi G, et al.: Evidence for the involvement of arachidonic acid metabolites in spontaneous and drug-induced contractions of rat urinary bladder. J Pharmacol Exp Ther 1984, 230:500–513.PubMedGoogle Scholar
  46. 46.
    Palea S, Toson G, Pietra C, et al.: Pharmacological characterization of thromboxane and prostanoid receptors in human isolated urinary bladder. Br J Pharmacol 1998, 124:865–872.PubMedCrossRefGoogle Scholar
  47. 47.
    Park JM, Yang T, Arend LJ, et al.: Obstruction stimulates COX-2 expression in bladder smooth muscle cells via increased mechanical stretch. Am J Physiol 1999, 276:F129–F136.PubMedGoogle Scholar
  48. 48.
    Bouchelouche K, Alvarez S, Andersen L, et al.: Monocyte chemoattractant protein-1 production by human detrusor smooth muscle cells. J Urol 2004, 171:462–466.PubMedCrossRefGoogle Scholar
  49. 49.
    Bouchelouche K, Alvarez S, Horn T, et al.: Human detrusor smooth muscle cells release interleukin-6, interleukin-8, and RANTES in response to proinflammatory cytokines interleukin-1beta and tumor necrosis factor-alpha. Urology 2006, 67:214–219.PubMedCrossRefGoogle Scholar
  50. 50.
    Takagi-Matsumoto H, Ng B, Tsukimi Y, Tajimi M: Effects of NSAIDs on bladder function in normal and cystitis rats: a comparison study of aspirin, indomethacin, and ketoprofen. J Pharmacol Sci 2004, 95:458–465.PubMedCrossRefGoogle Scholar
  51. 51.
    Angelico P, Guarneri L, Velasco C, et al.: Effect of cyclooxygenase inhibitors on the micturition reflex in rats: correlation with inhibition of cyclooxygenase isozymes. BJU Int 2006, 97:837–846.PubMedCrossRefGoogle Scholar
  52. 52.
    Erdogru T, Celik-Ozenci C, Seval Y, et al.: The restorative effect of a selective cyclooxygenase-2 inhibitor on urothelial cell-cell interactions after partial bladder outlet obstruction in rats. BJU Int 2005, 95:664–669.PubMedCrossRefGoogle Scholar
  53. 53.
    Meini S, Lecci A, Cucchi P, et al.: Inflammation modifies the role of cyclooxygenases in the contractile responses of the rat detrusor smooth muscle to kinin agonists. J Pharmacol Exp Ther 1998, 287:137–143.PubMedGoogle Scholar
  54. 54.
    Cardozo LD, Stanton SL: A comparison between bromocriptine and indomethacin in the treatment of detrusor instability. J Urol 1980, 123:399–401.PubMedGoogle Scholar
  55. 55.
    Cardozo LD, Stanton SL, Robinson H, Hole D: Evaluation of flurbiprofen in detrusor instability. Br Med J 1980, 280:281–282.PubMedCrossRefGoogle Scholar
  56. 56.
    Araki T, Yokoyama T, Kumon H: Effectiveness of a nonsteroidal anti-inflammatory drug for nocturia on patients with benign prostatic hyperplasia: a prospective non-randomized study of loxoprofen sodium 60 mg once daily before sleeping. Acta Med Okayama 2004, 58:45–49.PubMedGoogle Scholar
  57. 57.
    Di Silverio F, Bosman C, Salvatori M, et al.: Combination therapy with rofecoxib and finasteride in the treatment of men with lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia (BPH). Eur Urol 2005, 47:72–78; discussion 78–79.PubMedCrossRefGoogle Scholar
  58. 58.
    Verhamme KM, Dieleman JP, Van Wijk MA, et al.: Nonsteroidal anti-inflammatory drugs and increased risk of acute urinary retention. Arch Intern Med 2005, 165:1547–1551.PubMedCrossRefGoogle Scholar
  59. 59.
    Partin JV, Anglin IE, Kyprianou N: Quinazoline-based alpha 1-adrenoceptor antagonists induce prostate cancer cell apoptosis via TGF-beta signalling and I kappa B alpha induction. Br J Cancer 2003, 88:1615–1621.PubMedCrossRefGoogle Scholar

Copyright information

© Current Medicine Group LLC 2008

Authors and Affiliations

  1. 1.Mayo ClinicDivision of EpidemiologyRochesterUSA

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