Role of substance P in several models of bladder inflammation.

Substance P (SP) is a peptide found in the sensory nervous system which has multiple biologic effects including stimulation of muscle contraction, pain nociception, immune cell functions, plasma extravasation and a constellation of inflammatory effects. Here we investigate the role of SP in several animals models of bladder inflammation. Using the female Lewis rat, inflammation was induced using either xylene, lipopolysaccharide (LPS) or polyinosinic-polycytidylic acid (polyIC). Inflammation occurred rapidly (4 h) and was maintained in each model for at least 7 days. Each of these protocols decreased the bladder content of immunoreactive SP by approximately 50%, suggesting enhanced release. There was no change in the urinary frequency of these animals over 3 weeks, suggesting that urinary frequency changes are not mediated by acute inflammation. We also found that the SP receptor (NK1) antagonist, (-)CP96345, was unable to block the inflammation produced by polyIC, suggesting that SP is not an obligatory mediator of immune cell stimulation in this model.

17 beta-estradiol induced prostatitis in the rat is an autoimmune disease.

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 micrograms/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 10(7) 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+ T-cells. CONCLUSION: Our results demonstrate that hormonal imbalance and autoimmunity in male rats produce the symptoms of nonbacterial prostatitis.

Experimental autoimmune cystitis in the Lewis rat: a potential animal model for interstitial cystitis.

To develop an autoimmune animal model for interstitial cystitis (IC), we injected rats with Freund's adjuvant (CFA) containing bladder homogenate (experimentals) or CFA alone (shams). We observed a doubling of urinary frequency in the experimental animals over the shams (P = 0.004) and histopathologic changes (venular congestion) consistent with IC. Statistically significant bladder capacity changes were not found. Mast cell (MC) number was not statistically different between experimentals and controls but the number of MCs from section to adjacent section within the same animal's bladder did vary markedly, indicating the MC counts are not a reliable measure of disease in the rat bladder. Splenocytes cultured from the experimental animals and transferred to naive syngeneic recipients were capable of transferring the urinary frequency changes and vascular congestion while splenocytes from animals which did not develop the condition were without effect. In summary, we have developed and autoimmune model for IC consistent with the clinical features of IC. The features of this model can be transferred to naive syngeneic recipients via adoptive splenocyte transfer. The model will permit us to ask and answer important questions about the pathogenesis and treatment of the human disease.