17 beta-Estradiol Induced Prostatitis in the Rat is an Autoimmune Disease
Abstract
Purpose:
Studies suggest that alteration in steroid hormone levels may be one of the factors causing nonbacterial prostatitis (NBP) in rats. We hypothesized that hormonally induced prostatitis in the rat may be an autoimmune disease. Studies were carried out to prove this hypothesis.
Materials and Methods:
We injected 17 beta-estradiol (E2; 250 microgram/kg. subcutaneously) or vehicle into 1-year-old male rats for 30 days, and isolated and cultured the splenocytes in the presence of con-A (Experiment 1). Approximately 107 splenocytes were adoptively transferred into young naive syngeneic rats. To find out whether or not the inflammation is mediated by T-lymphocytes, a pure population of T-lymphocytes from E2 -treated 3-month-old rats was injected into young naive syngeneic rats (Experiment 2). To rule out the possibility that the inflammation was due to con-A itself, we cross-linked some T-cells with anti-CD3 antibody before adoptive transfer (Experiment 2).
Results:
The recipients of splenocytes from E2 -treated animals presented evidence of inflammation in terms of lymphocytic infiltration and presence of degranulated mast cells. Furthermore, we observed in these animals an increase in histamine-releasing peptide (HRP) levels, an indication of plasma extravasation. The T-cells stimulated by anti-CD3 antibody produced a similar degree of inflammation, thereby ruling out the possibility that the inflammation was due to con-A. The results also indicated that the immune response to antigen(s) is not dependent on the age of the animal but is dependent on a population of CD3 sup + T-cells.
Conclusion:
Our results demonstrate that hormonal imbalance and autoimmunity in male rats produce the symptoms of nonbacterial prostatitis.
References
- 1 :
Prostatitis and related disorders . In: Cambell's Urology. Edited by . Philadelphia: W. B. Saunders Co.1986. Google Scholar - 2 : The role of androgens and estrogens in the pathogenesis of experimental nonbacterial prostatitis. J. Urol.1988; 140: 1049. Link, Google Scholar
- 3 : An examination of research design effects on the association of testosterone and male aging: results of a meta-analysis. J. Clin. Epidemiol.1991; 44: 671. Google Scholar
- 4 : Trophic factors in aging. Should older people receive hormonal replacement therapy? Drugs Aging1994; 4: 492. Google Scholar
- 5 : Effect of aging on endogenous level of 5-alpha dihydrotestosterone, testosterone, estradiol and estrone in epithelium and stroma of normal and hyperplastic human prostate. J. Clin. Endocr. Metabol.1993; 77: 375. Google Scholar
- 6 : Alterations of estrogen metabolism in systemic lupus erythematosus. Arthritis Rheum.1979; 22: 1195. Google Scholar
- 7 : Adoptive transfer of murine autoimmune orchitis to naive recipients with immune lymphocytes. Cell. Immunol.1987; 106: 408. Google Scholar
- 8 : Solid phase anti-CD3 activation of murine tumor infiltrating lymphocytes. Cancer Res.1990; 50: 2587. Google Scholar
- 9 : Activation of human tumor-infiltrating lymphocytes by monoclonal antibodies directed to the CD3 complex. Cancer Res.1990; 50: 1138. Google Scholar
- 10 : Anti-CD3 antibody activation and cryopreservation of human lung lymphocytes derived from epithelial ovarian cancer. Jpn. J. Cancer Res.1992; 83: 1359. Google Scholar
- 11 : Stimulated rat mast cells generate histamine releasing peptide from albumin. Peptides1993; 14: 117. Google Scholar
- 12 : Activation of cytotoxic cells by syngeneic prostate antigen in experimental autoimmune vesiculoprostatitis. Autoimmunity1991; 9: 151. Google Scholar
- 13 : Development of a mouse model for nonbacterial prostatitis. J. Urol.1994; 152: 247. Link, Google Scholar
- 14 : Neutrophil recruitment by tumor necrosis factor from mast cells in immune complex peritonitis. Science1992; 258: 1957. Google Scholar
- 15 : Mast cell activation in sterile bladder and prostate inflammation. Int. Arch. Allergy Appl. Immunol.1990; 92: 281. Google Scholar
- 16 : Bacteriologic localization patterns in bacterial prostatitis and urethritis. Invest. Urol.1968; 5: 492. Google Scholar
- 17 : Combination finasteride and flutamide in advanced carcinoma of the prostate: effective therapy with minimal side effects. J. Urol.1995; 154: 1642. Link, Google Scholar
- 18 : Sex hormones, immune responses and autoimmune diseases. Am. J. Pathol.1985; 121: 531. Google Scholar
- 19 : Intraprostatic antibody deposition in chronic abacterial prostatitis. Br. J. Urol.1990; 65: 598. Crossref, Google Scholar
- 20 : HLA expression by benign and malignant prostatic epithelium: augmentation by interferon-gamma. J. Urol.1993; 150: 1289. Abstract, Google Scholar
Divisions of Urologic Transplantation and Surgery, and Research, Department of Surgery, and the Department of Pathology, University of Massachusetts Medical Center, Worcester, Massachusetts, and the Department of Pathology, Little Company of Mary Hospital, Chicago, Illinois.
