Preliminary study on urinary cytokine levels in interstitial cystitis: does intravesical bacille Calmette-Guérin treat interstitial cystitis by altering the immune profile in the bladder?

Abstract

Objectives. To obtain preliminary urinary cytokine data on subjects with active interstitial cystitis (IC), subjects with IC in remission after bacille Calmette-Guérin (BCG), and control (non-IC) subjects. IC is a severe, debilitating bladder disease of unknown etiology and no cure. In controlled clinical trials, intravesical BCG has been shown to be an effective and durable treatment for IC. The durability of this treatment led us to speculate on the mechanism by which intravesical BCG may treat IC. Evidence exists that IC may be mediated by an abnormal immune profile within the bladder. Intravesical BCG is known to stimulate the immune system of the bladder. Methods. Fresh voided urine was collected from 15 subjects with active IC, 9 subjects with IC who received intravesical BCG and had been in remission for an average of 2.6 years, and 11 non-IC subjects. The urine was immediately centrifuged, aliquoted, and frozen in liquid nitrogen. At the time of urine collection, a validated IC questionnaire was completed. The enzyme-linked immunosorbent assay technique was used to determine levels of urinary cytokines interleukin (IL)-2, IL-4, IL-6, IL-8, IL-10, IL-12, tumor necrosis factor (TNF), human granulocyte-macrophage colony stimulating factor (hGM-CSF), IL-1beta, and interferon-gamma (IFN-gamma). Results. Cytokines IL-4, IL-10, IL-12, TNF, hGM-CSF, IL-1beta, and IFN-gamma were not detected. Significant elevations in symptom scores and IL-2, IL-6, and IL-8 were found in the urine of subjects with active IC compared with subjects with IC in remission and control subjects. The urinary cytokine levels and symptom scores were identical in the IC group who had received BCG and the control group. Conclusions. Elevations in symptom scores and urinary cytokine levels were seen in subjects with active IC, suggesting an abnormal immune profile in this disease. Subjects with IC in remission after receiving BCG had identical cytokine levels and symptom scores as non-IC control subjects. Intravesical BCG may be effective in treating IC by correcting an aberrant immune imbalance in the bladder, leading to long-term symptomatic improvement. A prospective study is ongoing to further investigate the role of the immune system in IC.