Elevated tryptase, nerve growth factor, neurotrophin-3 and glial cell line-derived neurotrophic factor levels in the urine of interstitial cystitis and bladder cancer patients.

Abstract

The 2 prominent features of interstitial cystitis are pain and increased numbers of mast cells in the bladder. In this pilot study we determined the concentration of soluble mediators associated with activation of sensory neurons and/or mast cells that were present in the urine. The study groups included 4 interstitial cystitis patients, 7 kidney donors with no history of bladder disease as negative controls, 6 bladder cancer patients and 7 patients with urinary tract infection as reference controls. Urine samples were assayed for different soluble mediators using immunoassays for tryptase (a marker for mast cell activation), neurotrophic factors (markers of neuronal plasticity) and chemokines (markers of inflammatory cell activity). Results were normalized based on creatinine concentration. There was a marked increase in the average amounts of tryptase and 3 neurotrophic factors in patient urine. Interestingly, the mediator profile in the urine of bladder cancer patients was indistinguishable from that of interstitial cystitis patients with respect to these same 4 proteins. There was no difference between normal control and urinary tract infection urine samples. These findings may account for several clinical and pathological features found in interstitial cystitis and bladder cancer. Although preliminary due to the limited numbers of patients, they also suggest that increased levels of neurotrophin-3, nerve growth factor, glial cell line-derived neurotrophic factor and tryptase in the urine could serve as a basis for adjunct diagnosis, monitoring and treatment of interstitial cystitis.