Changes in cytokines and urothelial factors of urine in interstitial cystitis/painful bladder syndrome

Abstract

Interstitial cystitis/bladder pain syndrome (IC/BPS) is thought to have an autoimmune component due to increased prevalence of certain autoimmune conditions in the patients. Recent studies have revealed abnormalities in cytokine signaling in cultured urothelial cells of the urinary bladder. However, there is only scarce information on concentration of cytokines and some biomarkers, e.g., heparin-binding growth factor (HB-EGF) and epidermal growth factor (EGF), in the patients with IC/BPS. The purpose of present study was to determine concentrations of cytokines, HB-EGF and EGF in urine and their interrelations in patients with IC/BPS. 68 women with IC/BPS and 20 women without this disease (control group) were examined. The average age of women with IC/BPS was 54.2±12.4 years, the control group was 35.3±9.7 years. The morning urine samples were tested for interleukin contents (IL-1β, IL-6, IL-8), tumor necrosis factor-α (TNFα), as well as HB-EGF and EGF concentrations measured by ELISA technique. Statistical analysis of the obtained results was performed using Statistica software in Microsoft Excel. A relationship between the indexes was calculated with Pearson correlation quotient. The ratios for Th1/Th2 cytokines were calculated. Urination frequency, clinical symptoms including pollakiuria, nocturia and its urgency, were significantly more often in patients with IC/BPS compared to the control group (p 0.05-0.001). In patients with IC/BPS, the average levels of IL-1β, IL-8, IL-6 and TNFα exhibited, respectively, 2.4-, 2.3- and 2.0-fold increase over control values (p 0.05). The HB-EGF and EGF excretion in the urine was 2.3 times (p 0.05) over control levels. The IL-1β/IL-6 ratio averaged 1.16 in the group of patients with IC/BPS versus 0.95 in the control group, and the TNFα/IL-6 ratio was 1.0, respectively. There was a positive correlation between the levels of IL-1β and IL-6, TNFα (p 0.05), HB-EGF and EGF, and a negative correlation with IL-8 (p 0.01). In women with IC/BPS, there was a weak multidirectional correlation between IL-6 and other cytokines, as well as with HB-EGF and EGF contents. IL-8 levels in both groups showed weak correlation with other indexes. The TNFα amount weakly correlated with HB-EGF and EGF in IC/BPS. Based on the results obtained, one may state that, in IC/BPS, the excretion of pro-inflammatory cytokines was significantly increased, the balance of Th1/Th2 cytokines and contents of growth factors are disturbed. Expression of cytokines in combination with growth factors (HB-EGF and EGF) can be used to explain the pathophysiology of the clinical features in IC/BPS. Analysis of cytokine profiles may be used for differential diagnosis of IC/BPS and other disorders of urinary bladder.