Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

Experimental rodent models of prostatitis: limitations and potential

Prostate Cancer and Prostatic Diseases volume 10, pages 15–29 (2007)Cite this article

Abstract

Prostatitis is a polyetiological inflammation of the prostate gland in men characterized by pelvic pain, irritative voiding symptoms, and sexual dysfunction. Histologically prostatitis is characterized by poly- and mononuclear cell infiltrates (neutrophils, lymphocytes, macrophages and plasma cells) in the stromal connective tissue around the acini or ducts. Prostatitis is an important worldwide health problem in men. The pathogenesis and diagnostic criteria for the condition are obscure, with the result that the development of management programs for this condition has been hindered. Animal model(s) might be useful in elucidating mechanisms involved in the molecular pathogenesis of chronic nonbacterial prostatitis and chronic pelvic pain syndrome. Given that prostatitis might have a multifactorial etiology, several animal models with unique features may prove helpful. This review examines a number of experimental rodent models of prostatitis and evaluates their advantages and limitations.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Collins MM, Stafford RS, O'Leary MP, Barry MJ . How common is prostatitis? A national survey of physician visits. J Urol 1998; 159: 1224–1228.

    Article  CAS  PubMed  Google Scholar 

  2. Stamey T . Urinary tract infections in males. In: Stamey T (ed). Pathogenesis and Treatment of Urinary Tract Infections. Williams and Wilkins: Baltimore, MD, 1980, pp 342–429.

    Google Scholar 

  3. Moon TD, Hagen L, Heisey DM . Urinary symptomatology in younger men. Urology 1997; 50: 700–703.

    Article  CAS  PubMed  Google Scholar 

  4. Roberts RO, Lieber MM, Rhodes T, Girman CJ, Bostwick DG, Jacobsen SJ . Prevalence of a physician-assigned diagnosis of prostatitis: the Olmsted County Study of Urinary Symptoms and Health Status Among Men. Urology 1998; 51: 578–584.

    Article  CAS  PubMed  Google Scholar 

  5. Nickel JC, Downey J, Hunter D, Clark J . Prevalence of prostatitis-like symptoms in a population based study using the National Institutes of Health Chronic Prostatitis Symptom Index. J Urol 2001; 165: 842–845.

    Article  CAS  PubMed  Google Scholar 

  6. Mehik A, Hellstrom P, Lukkarinen O, Sarpola A, Jarvelin M . Epidemiology of prostatitis in Finnish men: a population-based cross-sectional study. BJU Int 2000; 86: 443–448.

    Article  CAS  PubMed  Google Scholar 

  7. Tan JK, Png DJ, Liew LC, Li MK, Wong ML . Prevalence of prostatitis-like symptoms in Singapore: a population based study. Singapore Med J 2002; 43: 189–193.

    CAS  PubMed  Google Scholar 

  8. Kunishima Y, Matsukawa M, Takahashi S, Itoh N, Hirose T, Furuya S et al. National institutes of health chronic prostatitis symptom index for Japanese men. Urology 2002; 60: 74–77.

    Article  PubMed  Google Scholar 

  9. Cheah PY, Liong HL, Yuen KH, Teh CL, Khor T, Yang JR et al. Chronic prostatitis: symptom survey with follow-up clinical evaluation. Urology 2003; 61: 60–64.

    Article  PubMed  Google Scholar 

  10. de la Rosette JJ, Hubregtse MR, Meuleman EJ, Stolk-Engelaar MV, Debruyne FM . Diagnosis and treatment of 409 patients with prostatitis syndromes. Urology 1993; 41: 301–307.

    Article  CAS  PubMed  Google Scholar 

  11. Krieger JN, Nyberg Jr L, Nickel JC . NIH consensus definition and classification of prostatitis. JAMA 1999; 282: 236–237.

    Article  CAS  PubMed  Google Scholar 

  12. Platz EA, De Marzo AM . Epidemiology of inflammation and prostate cancer. J Urol 2004; 171 (2 Part 2): S36–S40.

    PubMed  Google Scholar 

  13. Badalyan RR, Fanarjyan SV, Aghajanyan IG . Chlamydial and ureaplasmal infections in patients with nonbacterial chronic prostatitis. Andrologia 2003; 35: 263–265.

    Article  CAS  PubMed  Google Scholar 

  14. Nickel JC, Downey J, Pontari MA, Shoskes D, Zeitlin SI . A randomized placebo-controlled multicentre study to evaluate the safety and efficacy of finasteride for male chronic pelvic pain syndrome (category IIIA chronic nonbacterial prostatitis). BJU Int 2004; 93: 991–995.

    Article  CAS  PubMed  Google Scholar 

  15. Mercader M, Bodner BK, Moser MT, Kwon PS, Park ES, Manecke RG et al. T cell infiltration of the prostate induced by androgen withdrawal in patients with prostate cancer. Proc Natl Acad Sci USA 2001; 98: 14565–14570.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Shahed AR, Shoskes DA . Correlation of β-endorphin and PGE2 levels in prostatic fluid of chronic prostatitis patients with diagnosis and treatment response. J Urol 2001; 166: 1738–1741.

    Article  CAS  PubMed  Google Scholar 

  17. Miller LJ, Fischer KA, Goralnick SJ, Litt M, Burleson JA, Albertsen P et al. Nerve growth factor and chronic prostatitis/chronic pelvic pain syndrome. Urology 2002; 59: 603–608.

    Article  PubMed  Google Scholar 

  18. Alexander RB, Propert KJ, Schaeffer AJ, Landis JR, Nickel JC, O'Leary MP et al. Ciprofloxacin or tamsulosin in men with chronic prostatitis/chronic pelvic pain syndrome: a randomized, double-blind trial. Ann Int Med 2004; 141: 581–589.

    Article  CAS  PubMed  Google Scholar 

  19. Nickel JC, Narayan P, McKay J, Doyle C . Treatment of chronic prostatitis/chronic pelvic pain syndrome with tamsulosin: a randomized double blind trial. J Urol 2004; 171: 1594–1597.

    Article  CAS  PubMed  Google Scholar 

  20. Nickel JC . The three As of chronic prostatitis therapy: antibiotics, alpha-blockers and anti-inflammatories. What is the evidence? BJU Int 2004; 94: 1230–1233.

    Article  PubMed  Google Scholar 

  21. Kirby RS, Lowe D, Bultitude MI, Shuttleworth KE . Intra-prostatic urinary reflux: an aetiological factor in abacterial prostatitis. Br J Urol 1982; 54: 729–731.

    Article  CAS  PubMed  Google Scholar 

  22. Persson BE, Ronquist G, Ekblom M . Ameliorative effect of allopurinol on nonbacterial prostatitis: a parallel double-blind controlled study. J Urol 1996; 155: 961–964.

    Article  CAS  PubMed  Google Scholar 

  23. McNaughton CO, Wilt T . Allopurinol for chronic prostatitis. Cochrane Database Syst Rev 2002; 4: CD001041.

    Google Scholar 

  24. Jang TL, Schaeffer AJ . The role of cytokines in prostatitis. World J Urol 2003; 21: 95–99.

    Article  CAS  PubMed  Google Scholar 

  25. Alexander RB, Ponniah S, Hasday J, Hebel JR . Elevated levels of proinflammatory cytokines in the semen of patients with chronic prostatitis/chronic pelvic pain syndrome. Urology 1998; 52: 744–749.

    Article  CAS  PubMed  Google Scholar 

  26. Orhan I, Onur R, Ilhan N, Ardicoglu A . Seminal plasma cytokine levels in the diagnosis of chronic pelvic pain syndrome. Int J Urol 2001; 8: 495–499.

    Article  CAS  PubMed  Google Scholar 

  27. John H, Barghorn A, Funke G, Sulser T, Hailemariam S, Hauri D et al. Noninflammatory chronic pelvic pain syndrome: immunological study in blood, ejaculate and prostate tissue. Eur Urol 2001; 39: 72–78.

    Article  CAS  PubMed  Google Scholar 

  28. Nadler RB, Koch AE, Calhoun EA, Campbell PL, Pruden DL, Bennett CL et al. IL-1β and TNF-α in prostatic secretions are indicators in the evaluation of men with chronic prostatitis. J Urol 2000; 164: 214–218.

    Article  CAS  PubMed  Google Scholar 

  29. Miller LJ, Fischer KA, Goralnick SJ, Litt M, Burleson JA, Albertsen P et al. Interleukin-10 levels in seminal plasma: implications for chronic prostatitis-chronic pelvic pain syndrome. J Urol 2002; 167: 753–756.

    Article  CAS  PubMed  Google Scholar 

  30. Hochreiter WW, Nadler RB, Koch AE, Campbell PL, Ludwig M, Weidner W et al. Evaluation of the cytokines interleukin 8 and epithelial neutrophil activating peptide 78 as indicators of inflammation in prostatic secretions. Urology 2000; 56: 1025–1029.

    Article  CAS  PubMed  Google Scholar 

  31. Nishimura T, Abe H, Ito H, Ikeda K, Oka F, Yamamoto M . IL-1ra versus IL-1 levels in prostatic fluid from prostatitis patients. Urol Int 1998; 60: 92–96.

    Article  CAS  PubMed  Google Scholar 

  32. Shoskes DA, Albakri Q, Thomas K, Cook D . Cytokine polymorphisms in men with chronic prostatitis/chronic pelvic pain syndrome: association with diagnosis and treatment response. J Urol 2002; 168: 331–335.

    Article  CAS  PubMed  Google Scholar 

  33. Alexander RB, Brady F, Ponniah S . Autoimmune prostatitis: evidence of T cell reactivity with normal prostatic proteins. Urology 1997; 50: 893–899.

    Article  CAS  PubMed  Google Scholar 

  34. Batstone GR, Doble A, Gaston JS . Autoimmune T cell responses to seminal plasma in chronic pelvic pain syndrome (CPPS). Clin Exp Immunol 2002; 128: 302–307.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. John H, Maake C, Barghorn A, Zbinden R, Hauri D, Joller-Jemelka HI . Immunological alterations in the ejaculate of chronic prostatitis patients: clues for autoimmunity. Andrologia 2003; 35: 294–299.

    Article  CAS  PubMed  Google Scholar 

  36. Klyushnenkova EN, Link J, Oberle WT, Kodak J, Rich C, Vandenbark AA et al. Identification of HLA-DRB1*1501-restricted T-cell epitopes from prostate-specific antigen. Clin Cancer Res 2005; 11: 2853–2861.

    Article  CAS  PubMed  Google Scholar 

  37. Collins MM, MacDonald R, Wilt TJ . Diagnosis and treatment of chronic abacterial prostatitis: a systematic review. Ann Intern Med 2000; 133: 367–381.

    Article  Google Scholar 

  38. Collins MM, Pontari MA, O'Leary MP, Calhoun EA, Santanna J, Landis JR et al. Quality of life is impaired in men with chronic prostatitis: the chronic prostatitis collaborative research network. J Gen Intern Med 2001; 16: 656–662.

    Article  Google Scholar 

  39. Coussens LM, Werb Z . Inflammation and cancer. Nature 2002; 420: 860–867.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Gerstenbluth RE, Seftel AD, MacLennan GT, Rao RN, Corty EW, Ferguson K 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.

    Article  PubMed  Google Scholar 

  41. Palapattu GS, Sutcliffe S, Bastian PJ, Platz EA, De Marzo AM, Isaacs WB et al. Prostate carcinogenesis and inflammation: emerging insights. Carcinogenesis 2005; 26: 1170–1181.

    Article  CAS  PubMed  Google Scholar 

  42. Nelson WG, De Marzo AM, DeWeese TL, Isaacs WB . The role of inflammation in the pathogenesis of prostate cancer. J Urol 2004; 172 (5 Part 2): S6–S11.

    CAS  PubMed  Google Scholar 

  43. Sutcliffe S, Zenilman JM, Ghanem KG, Jadack RA, Sokoll LJ, Elliott DJ et al. Sexually transmitted infections and prostatic inflammation/cell damage as measured by serum prostate specific antigen concentration. J Urol 2006; 175: 1937–1942.

    Article  PubMed  Google Scholar 

  44. MacLennan GT, Eisenberg R, Fleshman RL, Taylor JM, Fu P, Resnick MI et al. The influence of chronic inflammation in prostatic carcinogenesis: a 5-year followup study. J Urol 2006; 176: 1012–1016.

    Article  PubMed  Google Scholar 

  45. Lam-Tse WK, Lernmark A, Drexhage HA . Animal models of endocrine/organ-specific autoimmune diseases: do they really help us to understand human autoimmunity? Springer Semin Immunopathol 2002; 24: 297–321.

    Article  CAS  PubMed  Google Scholar 

  46. Yang Y, Santamaria P . Lessons on autoimmune diabetes from animal models. Clin Sci (London) 2006; 110: 627–639.

    Article  CAS  Google Scholar 

  47. Borchers A, Ansari AA, Hsu T, Kono DH, Gershwin ME . The pathogenesis of autoimmunity in New Zealand mice. Semin Arthritis Rheum 2000; 29: 385–399.

    Article  CAS  PubMed  Google Scholar 

  48. Grigoriadis N, Tselios T, Deraos S, Orologas A, Deraos G, Matsoukas J et al. Animal models of central nervous system immune-mediated diseases: therapeutic interventions with bioactive peptides and mimetics. Curr Med Chem 2005; 12: 1513–1519.

    Article  CAS  PubMed  Google Scholar 

  49. Sauermann U . Making the animal model for AIDS research more precise: the impact of major histocompatibility complex (MHC) genes on pathogenesis and disease progression in SIV-infected monkeys. Curr Mol Med 2001; 1: 515–522.

    Article  CAS  PubMed  Google Scholar 

  50. Lubberts E, Koenders MI, van den Berg WB . The role of T-cell interleukin-17 in conducting destructive arthritis: lessons from animal models. Arthr Res Ther 2005; 7: 29–37.

    Article  CAS  Google Scholar 

  51. Ellinwood NM, Vite CH, Haskins ME . Gene therapy for lysosomal storage diseases: the lessons and promise of animal models. J Gene Med 2004; 6: 481–506.

    Article  CAS  PubMed  Google Scholar 

  52. Maragakis NJ, Rothstein JD . Glutamate transporters: animal models to neurologic disease. Neurobiol Dis 2004; 15: 461–473.

    Article  CAS  PubMed  Google Scholar 

  53. Grunig G, Kurup VP . Animal models of allergic bronchopulmonary aspergillosis. Front Biosci 2003; 8: e157–e171.

    Article  CAS  PubMed  Google Scholar 

  54. Lee A . Animal models of gastroduodenal ulcer disease. Baillieres Best Pract Res Clin Gastroenterol 2000; 14: 75–96.

    Article  CAS  PubMed  Google Scholar 

  55. Rubinstein G . Schizophrenia, infection and temperature. An animal model for investigating their interrelationships. Schizophr Res 1993; 10: 95–102.

    Article  CAS  PubMed  Google Scholar 

  56. McMahon AC, Kritharides L, Lowe HC . Animal models of atherosclerosis progression: current concepts. Curr Drug Targets Cardiovasc Haematol Disord 2005; 5: 433–440.

    Article  CAS  PubMed  Google Scholar 

  57. Luzzi GA . Chronic prostatitis and chronic pelvic pain in men: aetiology, diagnosis and management. J Eur Acad Dermatol Venereol 2002; 16: 253–256.

    Article  CAS  PubMed  Google Scholar 

  58. Sugimura Y, Cunha GR, Donjacour AA . Morphogenesis of ductal networks in the mouse prostate. Biol Reprod 1986; 34: 961–971.

    Article  CAS  PubMed  Google Scholar 

  59. Jesik CJ, Holland JM, Lee C . An anatomic and histologic study of the rat prostate. Prostate 1982; 3: 81–97.

    Article  CAS  PubMed  Google Scholar 

  60. Greenberg NM, DeMayo F, Finegold MJ, Medina D, Tilley WD, Aspinall JO et al. Prostate cancer in a transgenic mouse. Proc Natl Acad Sci USA 1995; 92: 3439–3443.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Pollard M, Luckert PH . Autochthonous prostate adenocarcinomas in Lobund-Wistar rats: a model system. Prostate 1987; 11: 219–227.

    Article  CAS  PubMed  Google Scholar 

  62. van Bokhoven A, Varella-Garcia M, Korch C, Johannes WU, Smith EE, Miller HL et al. Molecular characterization of human prostate carcinoma cell lines. Prostate 2003; 57: 205–225.

    Article  CAS  PubMed  Google Scholar 

  63. Lundgren R, Holmquist B, Hesselvik M, Muntzing J . Treatment of prostatitis in the rat. Prostate 1984; 5: 277–284.

    Article  CAS  PubMed  Google Scholar 

  64. Sharma OP, Adlercreutz H, Strandberg JD, Zirkin BR, Coffey DS, Ewing LL . Soy of dietary source plays a preventive role against the pathogenesis of prostatitis in rats. J Steroid Biochem Mol Biol 1992; 43: 557–564.

    Article  CAS  PubMed  Google Scholar 

  65. Keith IM, Jin J, Neal Jr D, Teunissen BD, Moon TD . Cell relationship in a Wistar rat model of spontaneous prostatitis. J Urol 2001; 166: 323–328.

    Article  CAS  PubMed  Google Scholar 

  66. Muntzing J, Sufrin G, Murphy GP . Prostatitis in the rat. Scand J Urol Nephrol 1979; 13: 17–22.

    Article  CAS  PubMed  Google Scholar 

  67. Naslund MJ, Strandberg JD, Coffey DS . The role of androgens and estrogens in the pathogenesis of experimental nonbacterial prostatitis. J Urol 1988; 140: 1049–1053.

    Article  CAS  PubMed  Google Scholar 

  68. Penna G, Amuchastegui S, Cossetti C, Aquilano F, Mariani R, Adorini L . Spontaneous and induced autoimmune prostatitis in the non-obese diabetic mouse. J Urol 2006; 175 (Suppl): 35.

    Article  Google Scholar 

  69. Nickel JC . Recommendations for the evaluation of patients with prostatitis. World J Urol 2003; 21: 75–81.

    Article  PubMed  Google Scholar 

  70. Nickel JC . Antibiotics for bacterial prostatitis. J Urol 2000; 163: 1407.

    Article  CAS  PubMed  Google Scholar 

  71. Nickel JC, Moon T . Chronic bacterial prostatitis: an evolving clinical enigma. Urology 2005; 66: 2–8.

    Article  PubMed  Google Scholar 

  72. Kaplan L, Lee C, Schaeffer AJ . Effect of castration on experimental bacterial prostatitis in rats. Prostate 1983; 4: 625–630.

    Article  CAS  PubMed  Google Scholar 

  73. Nickel JC, Olson ME, Barabas A, Benediktsson H, Dasgupta MK, Costerton JW . Pathogenesis of chronic bacterial prostatitis in an animal model. Br J Urol 1990; 66: 47–54.

    Article  CAS  PubMed  Google Scholar 

  74. Rippere-Lampe KE, Lang M, Ceri H, Olson M, Lockman HA, O'Brien AD . Cytotoxic necrotizing factor type 1-positive Escherichia coli causes increased inflammation and tissue damage to the prostate in a rat prostatitis model. Infect Immun 2001; 69: 6515–6519.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Rank RG, White HJ, Soloff BL, Barron AL . Cystitis associated with chlamydial infection of the genital tract in male guinea pigs. Sex Transm Dis 1981; 8: 203–210.

    Article  CAS  PubMed  Google Scholar 

  76. Jantos CA, Augustin J, Durchfeld-Meyer B, Baumgartner W, Schiefer HG . Experimental genital tract infection with Chlamydia psittaci (GPIC agent) in male rats. Infection 1998; 26: 126–130.

    Article  CAS  PubMed  Google Scholar 

  77. Seo SI, Lee SJ, Kim JC, Choi YJ, Kim SW, Hwang TK et al. Effects of androgen deprivation on chronic bacterial prostatitis in a rat model. Int J Urol 2003; 10: 485–491.

    Article  CAS  PubMed  Google Scholar 

  78. Cho YH, Lee SJ, Lee JY, Kim SW, Lee CB, Lee WY et al. Antibacterial effect of intraprostatic zinc injection in a rat model of chronic bacterial prostatitis. Int J Antimicrob Agents 2002; 19: 576–582.

    Article  CAS  PubMed  Google Scholar 

  79. Lee YS, Han CH, Kang SH, Lee SJ, Kim SW, Shin OR et al. Synergistic effect between catechin and ciprofloxacin on chronic bacterial prostatitis rat model. Int J Urol 2005; 12: 383–389.

    Article  PubMed  Google Scholar 

  80. Elkahwaji JE, Ott CJ, Janda LM, Hopkins WJ . Mouse model for acute bacterial prostatitis in genetically distinct inbred strains. Urology 2005; 66: 883–887.

    Article  PubMed  Google Scholar 

  81. Elkahwaji E, Zhong W, Janda LM, Bjorling DE, Bushman W . Chronic prostatic infection and inflammation induce reactive dysplasia and neoplasia in mice. J Urol 2006; 175 (Suppl): 258.

    Article  Google Scholar 

  82. Pacheco-Rupil B, Depiante-Depaoli M, Romero RM, Yantorno C . Experimental autoimmune damage to rat male accessory glands (MAG). Am J Reprod Immunol 1981; 1: 255–261.

    Article  Google Scholar 

  83. Donadio AC, Depiante-Depaoli M . Inflammatory cells and MHC class II antigens expression in prostate during time-course experimental autoimmune prostatitis development. Clin Immunol Immunopathol 1997; 85: 158–165.

    Article  CAS  PubMed  Google Scholar 

  84. Donadio AC, Gagliano H, Remedi MM, Nowotny E, Depiante-Depaoli M . Time-course study of cellular immune response and testosterone metabolism in an autoimmune model for chronic prostatic inflammation. J Urol 1998; 160: 1546–1550.

    Article  CAS  PubMed  Google Scholar 

  85. Maccioni M, Rivero V, Riera CM . Autoantibodies against rat prostate antigens. Association of specific IGG2b and IGG2c with the DTH response. J Autoimmun 1996; 9: 485–491.

    Article  CAS  PubMed  Google Scholar 

  86. Pacheco-Rupil B, Depiante-Depaoli M, Casadio B . Experimental autoimmune damage to rat male accessory glands. II. T cell requirement in adoptive transfer of specific tissue damage. Am J Reprod Immunol 1984; 5: 15–19.

    Article  CAS  PubMed  Google Scholar 

  87. Galmarini M, Ferro ME, Riera CM . Delayed hypersensitivity and lesions following isoimmunization with modified rat male accessory glands: kinetics of induction. J Reprod Immunol 1988; 13: 147–157.

    Article  CAS  PubMed  Google Scholar 

  88. Moron G, Maletto B, Ropolo A, Pistoresi-Palencia MC . Effect of aging on experimental autoimmune prostatitis: differential kinetics of development. Clin Immunol Immunopathol 1998; 87: 256–265.

    Article  CAS  PubMed  Google Scholar 

  89. Casas-Ingaramo A, Depiante-Depaoli M, Pacheco-Rupil B . Activation of cytotoxic cells by syngeneic prostate antigens in experimental autoimmune vesiculo-prostatitis. Autoimmunity 1991; 9: 151–157.

    Article  CAS  PubMed  Google Scholar 

  90. Orsilles MA, Depiante-Depaoli M . Oxidative stress-related parameters in prostate of rats with experimental autoimmune prostatitis. Prostate 1998; 34: 270–274.

    Article  CAS  PubMed  Google Scholar 

  91. Rivero VE, Iribarren P, Riera CM . Mast cells in accessory glands of experimentally induced prostatitis in male Wistar rats. Clin Immunol Immunopathol 1995; 74: 236–242.

    Article  CAS  PubMed  Google Scholar 

  92. Fong L, Ruegg CL, Brockstedt D, Engleman EG, Laus R . Induction of tissue-specific autoimmune prostatitis with prostatic acid phosphatase immunization: implications for immunotherapy of prostate cancer. J Immunol 1997; 159: 3113–3117.

    CAS  PubMed  Google Scholar 

  93. Maccioni M, Riera CM, Rivero VE . Identification of rat prostatic steroid binding protein (PSBP) as an immunosuppressive factor. J Reprod Immunol 2001; 50: 133–149.

    Article  CAS  PubMed  Google Scholar 

  94. Liu KJ, Chatta GS, Twardzik DR, Vedvick TS, True LD, Spies AG et al. Identification of rat prostatic steroid-binding protein as a target antigen of experimental autoimmune prostatitis: implications for prostate cancer therapy. J Immunol 1997; 159: 472–480.

    CAS  PubMed  Google Scholar 

  95. Maccioni M, Rivero VE, Riera CM . Prostatein (or rat prostatic steroid binding protein) is a major autoantigen in experimental autoimmune prostatitis. Clin Exp Immunol 1998; 112: 159–165.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Gilardoni MB, Rabinovich GA, Oviedo M, Depiante-Depaoli M . Prostate cancer induction in autoimmune rats and modulation of T cell apoptosis. J Exp Clin Cancer Res 1999; 18: 493–504.

    CAS  PubMed  Google Scholar 

  97. Keetch DW, Humphrey P, Ratliff TL . Development of a mouse model for nonbacterial prostatitis. J Urol 1994; 152: 247–250.

    Article  CAS  PubMed  Google Scholar 

  98. van Blokland SC, Versnel MA . Pathogenesis of Sjogren's syndrome: characteristics of different mouse models for autoimmune exocrinopathy. Clin Immunol 2002; 103: 111–124.

    Article  CAS  PubMed  Google Scholar 

  99. Damotte D, Colomb E, Cailleau C, Brousse N, Charreire J, Carnaud C . Analysis of susceptibility of NOD mice to spontaneous and experimentally induced thyroiditis. Eur J Immunol 1997; 27: 2854–2862.

    Article  CAS  PubMed  Google Scholar 

  100. Rivero VE, Cailleau C, Depiante-Depaoli M, Riera CM, Carnaud C . Non-obese diabetic (NOD) mice are genetically susceptible to experimental autoimmune prostatitis (EAP). J Autoimmun 1998; 11: 603–610.

    Article  CAS  PubMed  Google Scholar 

  101. Rivero V, Carnaud C, Riera CM . Prostatein or steroid binding protein (PSBP) induces experimental autoimmune prostatitis (EAP) in NOD mice. Clin Immunol 2002; 105: 176–184.

    Article  CAS  PubMed  Google Scholar 

  102. Taguchi O, Kojima A, Nishizuka Y . Experimental autoimmune prostatitis after neonatal thymectomy in the mouse. Clin Exp Immunol 1985; 60: 123–129.

    CAS  PubMed  PubMed Central  Google Scholar 

  103. Taguchi O, Nishizuka Y . Self tolerance and localized autoimmunity. Mouse models of autoimmune disease that suggest tissue-specific suppressor T cells are involved in self tolerance. J Exp Med 1987; 165: 146–156.

    Article  CAS  PubMed  Google Scholar 

  104. Taguchi O, Kontani K, Ikeda H, Kezuka T, Takeuchi M, Takahashi T et al. Tissue-specific suppressor T cells involved in self-tolerance are activated extrathymically by self-antigens. Immunology 1994; 82: 365–369.

    CAS  PubMed  PubMed Central  Google Scholar 

  105. Sakaguchi S, Sakaguchi N, Asano M, Itoh M, Toda M . Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J Immunol 1995; 155: 1151–1164.

    CAS  PubMed  Google Scholar 

  106. Sakaguchi S . Naturally arising CD4+ regulatory t cells for immunologic self-tolerance and negative control of immune responses. Annu Rev Immunol 2004; 22: 531–562.

    Article  CAS  PubMed  Google Scholar 

  107. Bagavant H, Thompson C, Ohno K, Setiady Y, Tung KS . Differential effect of neonatal thymectomy on systemic and organ-specific autoimmune disease. Int Immunol 2002; 14: 1397–1406.

    Article  CAS  PubMed  Google Scholar 

  108. Bagavant H, Tung KS . Failure of CD25+ T cells from lupus-prone mice to suppress lupus glomerulonephritis and sialoadenitis. J Immunol 2005; 175: 944–950.

    Article  CAS  PubMed  Google Scholar 

  109. Kojima A, Tanaka-Kojima Y, Sakakura T, Nishizuka Y . Spontaneous development of autoimmune thyroiditis in neonatally thymectomized mice. Lab Invest 1976; 34: 550–557.

    CAS  PubMed  Google Scholar 

  110. Taguchi O, Nishizuka Y, Sakakura T, Kojima A . Autoimmune oophoritis in thymectomized mice: detection of circulating antibodies against oocytes. Clin Exp Immunol 1980; 40: 540–553.

    CAS  PubMed  PubMed Central  Google Scholar 

  111. Taguchi O, Nishizuka Y . Autoimmune oophoritis in thymectomized mice: T cell requirement in adoptive cell transfer. Clin Exp Immunol 1980; 42: 324–331.

    CAS  PubMed  PubMed Central  Google Scholar 

  112. Taguchi O, Nishizuka Y . Experimental autoimmune orchitis after neonatal thymectomy in the mouse. Clin Exp Immunol 1981; 46: 425–434.

    CAS  PubMed  PubMed Central  Google Scholar 

  113. Barrett SP, van Driel IR, Tan SS, Alderuccio F, Toh BH, Gleeson PA . Expression of a gastric autoantigen in pancreatic islets results in non-destructive insulitis after neonatal thymectomy. Eur J Immunol 1995; 25: 2686–2694.

    Article  CAS  PubMed  Google Scholar 

  114. Linsley PS, Brady W, Urnes M, Grosmaire LS, Damle NK, Ledbetter JA . CTLA-4 is a second receptor for the B cell activation antigen B7. J Exp Med 1991; 174: 561–569.

    Article  CAS  PubMed  Google Scholar 

  115. Thompson CB, Allison JP . The emerging role of CTLA-4 as an immune attenuator. Immunity 1997; 7: 445–450.

    Article  CAS  PubMed  Google Scholar 

  116. Chambers CA, Allison JP . Costimulatory regulation of T cell function. Curr Opin Cell Biol 1999; 11: 203–210.

    Article  CAS  PubMed  Google Scholar 

  117. Leach DR, Krummel MF, Allison JP . Enhancement of antitumor immunity by CTLA-4 blockade. Science 1996; 271: 1734–1736.

    Article  CAS  PubMed  Google Scholar 

  118. Kwon ED, Hurwitz AA, Foster BA, Madias C, Feldhaus A, Greenberg NM et al. Manipulation of T cell costimulatory and inhibitory signals for immunotherapy of prostate cancer. Proc Natl Acad Sci USA 1997; 94: 8099–8103.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Yang YF, Zou JP, Mu J, Wijesuriya R, Ono S, Walunas T et al. Enhanced induction of antitumor T-cell responses by cytotoxic T lymphocyte-associated molecule-4 blockade: the effect is manifested only at the restricted tumor-bearing stages. Cancer Res 1997; 57: 4036–4041.

    CAS  PubMed  Google Scholar 

  120. Mokyr MB, Kalinichenko T, Gorelik L, Bluestone JA . Realization of the therapeutic potential of CTLA-4 blockade in low-dose chemotherapy-treated tumorbearing mice. Cancer Res 1998; 58: 5301–5304.

    CAS  PubMed  Google Scholar 

  121. Hurwitz AA, Foster BA, Kwon ED, Truong T, Choi EM, Greenberg NM et al. Combination immunotherapy of primary prostate cancer in a transgenic mouse model using CTLA-4 blockade. Cancer Res 2000; 60: 2444–2448.

    CAS  PubMed  Google Scholar 

  122. Zhang J, Thomas TZ, Kasper S, Matusik RJ . A small composite probasin promoter confers high levels of prostate-specific gene expression through regulation by androgens and glucocorticoids in vitro and in vivo. Endocrinology 2000; 141: 4698–4710.

    Article  CAS  PubMed  Google Scholar 

  123. Andriani F, Nan B, Yu J, Li X, Weigel NL, McPhaul MJ et al. Use of the probasin promoter ARR2PB to express Bax in androgen receptor-positive prostate cancer cells. J Natl Cancer Inst 2001; 93: 1314–1324.

    Article  CAS  PubMed  Google Scholar 

  124. Lees JR, Charbonneau B, Hayball JD, Diener K, Brown M, Matusik R et al. T-cell recognition of a prostate specific antigen is not sufficient to induce prostate tissue destruction. Prostate 2006; 66: 578–590.

    Article  CAS  PubMed  Google Scholar 

  125. Kurts C, Carbone FR, Barnden M, Blanas E, Allison J, Heath WR et al. CD4Þ T-cell help impairs CD8Þ T-cell deletion induced by cross-presentation of self-antigens and favors autoimmunity. J Exp Med 1997; 186: 2057–2062.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Naslund MJ, Coffey DS . The differential effects of neonatal androgen, estrogen and progesterone on adult rat prostate growth. J Urol 1986; 136: 1136–1140.

    Article  CAS  PubMed  Google Scholar 

  127. Stoker TE, Robinette CL, Cooper RL . Perinatal exposure to estrogenic compounds and the subsequent effects on the prostate of the adult rat: evaluation of inflammation in the ventral and lateral lobes. Reprod Toxicol 1999; 13: 463–472.

    Article  CAS  PubMed  Google Scholar 

  128. Prins GS . Neonatal estrogen exposure induces lobe-specific alterations in adult rat prostate androgen receptor expression. Endocrinology 1992; 130: 3703–3714.

    Article  CAS  PubMed  Google Scholar 

  129. Robinette CL . Sex-hormone-induced inflammation and fibromuscular proliferation in the rat lateral prostate. Prostate 1988; 12: 271–286.

    Article  CAS  PubMed  Google Scholar 

  130. Harris MT, Feldberg RS, Lau KM, Lazarus NH, Cochrane DE . Expression of proinflammatory genes during estrogen-induced inflammation of the rat prostate. Prostate 2000; 44: 19–25.

    Article  CAS  PubMed  Google Scholar 

  131. Abbas AK, Murphy KM, Sher A . Functional diversity of helper T lymphocytes. Nature 1996; 383: 787–793.

    Article  CAS  PubMed  Google Scholar 

  132. Quan TE, Cowper SE, Bucala R . The role of circulating fibrocytes in fibrosis. Curr Rheumatol Rep 2006; 8: 145–150.

    Article  CAS  PubMed  Google Scholar 

  133. Wilson MJ, Woodson M, Wiehr C, Reddy A, Sinha AA . Matrix metalloproteinases in the pathogenesis of estradiol-induced nonbacterial prostatitis in the lateral prostate lobe of the Wistar rat. Exp Mol Pathol 2004; 77: 7–17.

    Article  CAS  PubMed  Google Scholar 

  134. Seethalakshmi L, Bala RS, Malhotra RK, Austin-Ritchie T, Miller-Graziano C, Menon M et al. 17 beta-estradiol induced prostatitis in the rat is an autoimmune disease. J Urol 1996; 156: 1838–1842.

    Article  CAS  PubMed  Google Scholar 

  135. Offner H . Neuroimmunoprotective effects of estrogen and derivatives in experimental autoimmune encephalomyelitis: therapeutic implications for multiple sclerosis. J Neurosci Res 2004; 78: 603–624.

    Article  CAS  PubMed  Google Scholar 

  136. Paterson PY . Demyelinating diseases of the central peripheral nervous systems. In: Swanborg RH, Sampter M, Talmage DW, Frank MM, Austen KF, Claman HN (eds). Immunological Diseases. Little, Brown and Co: Boston, 1988, pp 1877–1916.

    Google Scholar 

  137. Matejuk A, Dwyer J, Hopke C, Vandenbark AA, Offner H . Opposing roles for TGF-beta1 and TGF-beta3 isoforms in experimental autoimmune encephalomyelitis. Cytokine 2003; 25: 45–51.

    Article  CAS  Google Scholar 

  138. Polanczyk MJ, Carson BD, Subramanian S, Afentoulis M, Vandenbark AA, Ziegler SF et al. Cutting edge: estrogen drives expansion of the CD4+CD25+ regulatory T cell compartment. J Immunol 2004; 173: 2227–2230.

    Article  CAS  PubMed  Google Scholar 

  139. Polanczyk MJ, Hopke C, Huan J, Vandenbark AA, Offner H . Enhanced FoxP3 expression and Treg cell function in pregnant and estrogen-treated mice. J Neuroimmunol 2005; 170: 85–92.

    Article  CAS  PubMed  Google Scholar 

  140. Tangbanluekal L, Robinette CL . Prolactin mediates estradiol-induced inflammation in the lateral prostate of Wistar rats. Endocrinology 1993; 132: 2407–2416.

    Article  CAS  PubMed  Google Scholar 

  141. Suwa T, Nyska A, Peckham JC, Hailey JR, Mahler JF, Haseman JK et al. A retrospective analysis of background lesions and tissue accountability for male accessory sex organs in Fischer-344 rats. Toxicol Pathol 2001; 29: 467–478.

    Article  CAS  PubMed  Google Scholar 

  142. Stoker TE, Cooper RL, Laws SC, Robinette CL . Elevated prolactin (PRL) prior to puberty and the development of prostatitis in adult Wistar rats. Toxicologist 1999; 43: 145.

    Google Scholar 

  143. Stoker TE, Robinette CL, Britt BH, Laws SC, Cooper RL . Prepubertal exposure to compounds that increase prolactin secretion in the male rat: effects on the adult prostate. Biol Reprod 1999; 61: 1636–1643.

    Article  CAS  PubMed  Google Scholar 

  144. Shyr SW, Crowley WR, Grovenor CE . Effect of neonatal prolactin deficiency on prepubertal tuberoinfundibular and tuberohypophyseal dopaminergic neuronal activity. Endocrinology 1986; 119: 1217–1221.

    Article  CAS  PubMed  Google Scholar 

  145. Stoker TE, Robinette CL, Cooper RL . Maternal exposure to atrazine during lactation suppresses suckling-induced prolactin release and results in prostatitis in the adult offspring. Toxicol Sci 1999; 52: 68–79.

    Article  CAS  PubMed  Google Scholar 

  146. Gilleran JP, Putz O, DeJong M, DeJong S, Birch L, Pu Y et al. The role of prolactin in the prostatic inflammatory response to neonatal estrogen. Endocrinology 2003; 144: 2046–2054.

    Article  CAS  PubMed  Google Scholar 

  147. Thompson SA, Johnson MP, Brooks CL . Biochemical and immunohistochemical characterization of prolactin binding in rat ventral, lateral, and dorsal prostate lobes. Prostate 1982; 3: 45–58.

    Article  CAS  PubMed  Google Scholar 

  148. Reiter E, Hennuy B, Bruyninx M, Cornet A, Klug M, McNamara M et al. Effects of pituitary hormones on the prostate. Prostate 1999; 38: 159–165.

    Article  CAS  PubMed  Google Scholar 

  149. Berczi I . Pituitary hormones and immune function. Acta Paediatr 1997; 423 (Suppl): 70–75.

    Article  CAS  Google Scholar 

  150. Vykhovanets EV, Resnick MI, Marengo SR . The healthy rat prostate contains high levels of natural killer-like cells and unique subsets of CD4+ helper-inducer T cells: implications for prostatitis. J Urol 2005; 173: 1004–1010.

    Article  PubMed  Google Scholar 

  151. Vykhovanets EV, Resnick MI, Marengo SR . Intraprostatic lymphocyte profiles in aged Wistar rats with estradiol induced prostate inflammation. J Urol 2006; 175: 1534–1540.

    Article  CAS  PubMed  Google Scholar 

  152. Bostwick DG, de la Roza G, Dundore P, Corica FA, Iczkowski KA . Intraepithelial and stromal lymphocytes in the normal human prostate. Prostate 2003; 55: 187–193.

    Article  PubMed  Google Scholar 

  153. Godfrey DI, MacDonald HR, Kronenberg M, Smyth MJ, Van Kaer L . NKT cells: what's in a name? Nat Rev Immunol 2004; 4: 231–237.

    Article  CAS  PubMed  Google Scholar 

  154. Yoshimoto T, Paul WE . CD4pos, NK1.1pos T cells promptly produce interleukin-4 in response to in vivo challenge with anti-CD3. J Exp Med 1994; 179: 1285–1295.

    Article  CAS  PubMed  Google Scholar 

  155. Iwakoshi NN, Greiner DL, Rossini AA, Mordes JP . Diabetes prone BB rats are severely deficient in natural killer T cells. Autoimmunity 1999; 31: 1–14.

    Article  CAS  PubMed  Google Scholar 

  156. Shao H, Van Kaer L, Sun SL, Kaplan HJ, Sun D . Infiltration of the inflamed eye by NKT cells in a rat model of experimental autoimmune uveitis. J Autoimmun 2003; 21: 37–45.

    Article  CAS  PubMed  Google Scholar 

  157. Tori M, Ito T, Yumiba T, Maeda A, Sawai T, Miyasaka M et al. Significant role of intragraft lymphoid tissues in preventing insulin-dependent diabetes mellitus recurrence in whole pancreaticoduodenal transplantation. Microsurgery 1999; 19: 338–343.

    Article  CAS  PubMed  Google Scholar 

  158. Seddon B, Mason D . Peripheral autoantigen induces regulatory T cells that prevent autoimmunity. J Exp Med 1999; 189: 877–882.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. Saoudi A, Seddon B, Fowell D, Mason D . The thymus contains a high frequency of cells that prevent autoimmune diabetes on transfer into prediabetic recipients. J Exp Med 1996; 184: 2393–2398.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  160. Xystrakis E, Bernard I, Dejean AS, Alsaati T, Druet P, Saoudi A . Alloreactive CD4T lymphocytes responsible for acute and chronic graft-versus-host disease are contained within the CD45RChigh but not the CD45RClow subset. Eur J Immunol 2004; 34: 408–417.

    Article  CAS  PubMed  Google Scholar 

  161. Montironi R, Pomante R, Diamanti L, Magi-Galluzzi C . Apoptosis in prostatic adenocarcinoma following complete androgen ablation. Urol Int 1998; 60 (Suppl 1): 25–29.

    Article  PubMed  Google Scholar 

  162. Pakarainen T, Zhang FP, Makela S, Poutanen M, Huhtaniemi I . Testosterone replacement therapy induces spermatogenesis and partially restores fertility in luteinizing hormone receptor knockout mice. Endocrinology 2005; 146: 596–606.

    Article  CAS  PubMed  Google Scholar 

  163. Zhang FP, Poutanen M, Wilbertz J, Huhtaniemi I . Normal prenatal but arrested postnatal sexual development of luteinizing hormone receptor knockout (LuRKO) mice. Mol Endocrinol 2001; 15: 172–183.

    Article  CAS  PubMed  Google Scholar 

  164. Zhang FP, Pakarainen T, Zhu F, Poutanen M, Huhtaniemi I . Molecular characterization of postnatal development of testicular steroidogenesis in luteinizing hormone receptor knockout mice. Endocrinology 2004; 145: 1453–1463.

    Article  CAS  PubMed  Google Scholar 

  165. Lei ZM, Mishra S, Zou W, Xu B, Foltz M, Li X et al. Targeted disruption of luteinizing hormone/human chorionic gonadotropin receptor gene. Mol Endocrinol 2001; 15: 184–200.

    Article  CAS  PubMed  Google Scholar 

  166. Drago JR . The induction of NB rat prostatic carcinomas. Anticancer Res 1984; 4: 255–256.

    CAS  PubMed  Google Scholar 

  167. Gatenbeck L, Aronsson A, Dahlgren S, Johansson B, Stromberg L . Stress stimuli-induced histopathological changes in the prostate: an experimental study in the rat. Prostate 1987; 11: 69–76.

    Article  CAS  PubMed  Google Scholar 

  168. Aronsson A, Dahlgren S, Gatenbeck L, Stromberg L . Predictive sites of inflammatory manifestation in the prostatic gland: an experimental study on nonbacterial prostatitis in the rat. Prostate 1988; 13: 17–24.

    Article  CAS  PubMed  Google Scholar 

  169. Lang MD, Nickel JC, Olson ME, Howard SR, Ceri H . Rat model of experimentally induced abacterial prostatitis. Prostate 2000; 45: 201–206.

    Article  CAS  PubMed  Google Scholar 

  170. Kwon SM, Kim SI, Chun DC, Cho NH, Chung BC, Park BW et al. Development of rat prostatitis model by oral administration of isoflavone and its characteristics. Yonsei Med J 2001; 42: 395–404.

    Article  CAS  PubMed  Google Scholar 

  171. Takechi S, Yokoyama M, Tanji N, Nishio S, Araki N . Nonbacterial prostatitis caused by partial urethral obstruction in the rat. Urol Res 1999; 27: 346–350.

    Article  CAS  PubMed  Google Scholar 

  172. Young HH, Geraghty JT, Stevens AR . Chronic prostatitis. An experimental and clinical study with an analysis of 358 cases. Johns Hopkins Hospital Rep 1906; 13: 271–384.

    Google Scholar 

  173. Nickel JC, Bostwick DG, Somerville MC . Lack of relationship between clinical prostatitis and prostate inflammation: baseline data from the reduce trail. J Urol 2006; 175 (Suppl): 31.

    Article  Google Scholar 

Download references

Acknowledgements

Financial Support: Supported by the Sullivan Foundation for the Study of Prostatitis and The James & Eilleen Dicke Research Endowment funds.

Author information

Authors and Affiliations

  1. Department of Urology, Case Western Reserve University & University Hospitals of Cleveland, Cleveland, OH, USA

    E V Vykhovanets, M I Resnick & S Gupta

  2. Department of Pathology, Case Western Reserve University & University Hospitals of Cleveland, Cleveland, OH, USA

    G T MacLennan

  3. Ireland Cancer Center, Cleveland, OH, USA

    M I Resnick, G T MacLennan & S Gupta

Authors
  1. E V Vykhovanets
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M I Resnick
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. G T MacLennan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S Gupta
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to S Gupta.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Vykhovanets, E., Resnick, M., MacLennan, G. et al. Experimental rodent models of prostatitis: limitations and potential. Prostate Cancer Prostatic Dis 10, 15–29 (2007). https://doi.org/10.1038/sj.pcan.4500930

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.pcan.4500930

Keywords

This article is cited by

Search

Advanced search

Quick links