Concentrations of specific epithelial growth factors in the urine of interstitial cystitis patients and controls

Purpose: Interstitial cystitis (IC) is a chronic bladder disease for which the etiology is unknown. Because the bladder epithelium is often abnormal in IC, we determined whether the levels of specific urine growth factors postulated to be important for bladder epithelial proliferation are altered in IC. Materials and Methods: ELISAs were used to determine levels of epidermal growth factor (EGF), insulin-like growth factor 1 (IGF1), insulin-like growth factor binding protein 3 (IGFBP3), and heparin binding epidermal growth factor-like growth factor (HB-EGF) in urine specimens from women with IC, asymptomatic women without bladder disease, and women with bacterial cystitis. Results: Urine HB-EGF levels were specifically and significantly decreased in IC patients as compared to asymptomatic controls or patients with bacterial cystitis, whether expressed as concentration (amount per volume of urine) or the amount relative to urine creatinine in each specimen. In contrast, urine EGF, IGF1, and IGFBP3 levels were all significantly elevated in IC patients compared to asymptomatic controls. Further, the amounts of urine EGF and IGF1 were also elevated in IC patients as compared to patients with bacterial cystitis, and urine IGFBP3 levels were significantly elevated when expressed per milligram of urine creatinine. Conclusions: These findings indicate that complex changes in the levels of urine epithelial cell growth factors (EGF, IGF1, and HB-EGF) and a growth factor binding protein (IGFBP3) are associated with IC. While EGF, IGF1, and IGFBP3 levels are either the same or increased in the urine of IC patients as compared to patients with bacterial cystitis or asymptomatic controls, HB-EGF levels are significantly decreased in the urine of IC patients. Understanding the reasons for these changes may lead to understanding the pathogenesis of this disorder.