Increased apoptosis and suburothelial inflammation in patients with ketamine-related cystitis: a comparison with non-ulcerative interstitial cystitis and controls

Abstract

Objective: To investigate the suburothelial inflammation and urothelial dysfunction that occurs with ketamine-related cystitis (KC) and interstitial cystitis/bladder pain syndrome (IC/BPS).

Patients and methods: Bladder tissues from 16 patients with KC, 17 patients with IC/BPS and 10 control subjects were analysed. Immunofluorescence staining of the junction protein E-cadherin was carried out, and tryptase levels and a TUNEL assay were used to assess mast-cell activation and urothelial apoptosis, respectively. The fluorescence intensity of E-cadherin was measured using the ImageJ method. The percentages of activated mast cells and apoptotic cells were calculated as positive cells per unit area (4 μm(2) ).

Results: The mean (sd) ages of the patients in the KC, IC/BPS and control groups were 25.0 (3.8), 41.3 (13.7) and 50.5 (9.6) years, respectively (P < 0.05). The mean (sd) distributions of E-cadherin in KC (10.1 [11.2]) and IC/BPS (25.1 [16.3]) tissues were significantly lower than in the control tissues (42.4 [16.7]; both P < 0.05). The mean (sd) number of activated mast cells, measured by tryptase signals in the KC (6.5 [3.7]) and IC/BPS (4.6 [3.0]) tissues, were significantly higher than in the control tissues (1.3 [1.12]; both P < 0.05). TUNEL staining showed a significantly higher mean (sd) number of apoptotic cells in KC (4.4 [2.5]) and IC/BPS (2.4 [1.7]) tissues than in control tissues (0.1 [0.3]; both P < 0.05). Tissues from the KC bladders had significantly lower expression of E-cadherin (P = 0.024) and significantly higher numbers of apoptotic cells (P = 0.02) compared with the IC/BPS bladder tissues. Greater numbers of apoptotic cells and lower expression levels of E-cadherin significantly correlated with maximum bladder capacity in the overall patient samples (P < 0.05).

Conclusions: KC and IC/BPS tissues both showed defective junction protein, increased suburothelial inflammation and increased urothelial cell apoptosis. Decreased expression of E-cadherin and increased apoptosis were more severe in KC than in IC/BPS bladder tissues and these findings were associated with the clinical symptoms of KC and IC/BPS.

Keywords: apoptosis; bladder dysfunction; inflammation; ketamine; urothelium.