Increased urinary leukotriene E4 and eosinophil protein X excretion in patients with interstitial cystitis

Purpose: The role of cysteinyl containing leukotriene C4, D4 and E4, and eo sinophil protein X in interstitial cystitis is unknown. Leukotriene E4, the end product of cysteinyl containing leukotrienes, and eosinophil protein X are markers of the activation of mast cells and eosinophils, respectively. Cysteinyl containing leukotrienes are potent and specific chemoattractants for eosinophils. We compared the urinary excretion of leukotriene E4 and e osinophil protein X in patients with interstitial cystitis and in healthy c ontrols. Materials and Methods: Morning spot urine samples from nine patients with i nterstitial cystitis who fulfilled National Institute of Diabetes and Diges tive and Kidney Diseases criteria were collected on the day of cystoscopy w ith biopsies. Aliquots of urine specimens were immediately centrifuged and the supernatants were stored at -80C until use. Urine samples from 9 health y women served as controls. Urinary leukotriene E4 and eosinophil protein X were measured by enzyme immunoassay and radioimmunoassay, respectively. Al l determinations were performed in duplicate and normalized to urine creati nine. Results: Leukotriene E4 and eosinophil protein X were significantly increas ed in the morning urine of patients with interstitial cystitis compared wit h controls. The mean urinary excretion of leukotriene E4 plus or minus stan dard deviation was 148.8 +/- 62.5 and 62.2 +/- 17.5 ng./mmol. creatinine in patients and controls (p = 0.0013), while the mean urinary excretion of eo sinophil protein X was 109.71 +/- 70.4 and 43.7 +/- 22.0 mug./mmol. creatin ine, respectively (p = 0.01). All urine cultures were negative. The mean ma st cell count in detrusor biopsies in the interstitial cystitis group was 4 1 cells per mm.(2) (range 5 to 84). Eosinophilic granulocytes were occasion ally observed in the submucosa but not in the detrusor. Conclusions: Our study shows that patients with interstitial cystitis and d etrusor mastocytosis have increased urinary leukotriene E4 and eosinophil p rotein X. It is possible that cysteinyl containing leukotrienes and eosinop hil protein X are involved in the pathogenesis of interstitial cystitis. Ur inary leukotriene E4 and eosinophil protein X may be useful markers for ass essing the grade of activation of mast cells and eosinophils in patients wi th interstitial cystitis and/or for confirming the diagnosis. However, it r emains to be investigated whether the increase in urinary leukotriene E4 an d eosinophil protein X correlates with interstitial cystitis symptoms.