Cyclosporine A and pentosan polysulfate sodium for the treatment of interstitial cystitis: a randomized comparative study

PURPOSE: In a previous retrospective analysis, cyclosporine A (CyA) was highly efficient in treating patients with interstitial cystitis. A prospective randomized study with this immunosuppressive agent was warranted. We compared CyA to pentosan polysulfate sodium (PPS) in patients with interstitial cystitis. MATERIALS AND METHODS: A total of 64 patients with interstitial cystitis meeting the National Institute of Diabetes and Digestive and Kidney Diseases criteria were enrolled in a randomized prospective study. Patients were randomized in a 1:1 ratio to 1.5 mg/kg CyA twice daily (27 women, 5 men) or 100 mg PPS 3 times daily (26 women, 6 men) for a period of 6 months. The primary end point was daily micturition frequency, and secondary end points were mean and maximal voided volume, number of nocturia episodes, O'Leary-Sant symptom and problem indexes, visual analogue scale for pain, and subjective global response assessment. RESULTS: CyA was superior to PPS in all clinical outcome parameters measured at 6 months. Micturition frequency in 24 hours was significantly reduced in the CyA arm compared to the PPS arm (-6.7 +/- 4.7 vs -2.0 +/- 5.1 times). The clinical response rate (according to global response assessment) was 75% for CyA compared to 19% for PPS (p <0.001). Although there were more adverse events in the CyA arm than in the PPS arm, 29 patients completed the 6-month followup in both groups. CONCLUSIONS: CyA is more effective than PPS in interstitial cystitis.     

Potassium sensitivity test (PST) as a measurement of treatment efficacy of painful bladder syndrome/interstitial cystitis: a prospective study with cyclosporine A and pentosan polysulfate sodium

AIMS: Potassium sensitivity test (PST) has been used as an optional tool in diagnosing painful bladder syndrome/interstitial cystitis (PBS/IC). The role of PST in the follow-up of patients with PBS/IC is elusive. We performed PST before and after treatment of PBS/IC with cyclosporine A (CyA) or pentosan polysulfate sodium (PPS), to test whether the result of repeated PST correlates with alleviation of PBS/IC-related symptoms. MATERIALS AND METHODS: Sixty-four patients who participated in a randomized clinical study comparing CyA and PPS in the treatment of PBS/IC were recruited to the present study. Patients underwent 0.4 M PST before and after 6 months of treatment. The primary end point was a change from positive PST to negative among patients who responded to both treatments determined by global response assessment (GRA). RESULTS: Potassium sensitivity test (PST) was more likely to change from positive to negative among patients who responded to their treatment according to GRA (P < 0.001). The PST change follows the clinical course (ICSI score, voiding frequency, VAS score), which was more beneficial in the CyA-treated patients. CONCLUSIONS: Potassium sensitivity test (PST) reflects symptom severity of PBS/IC patients. Change of pre-treatment positive PST to negative correlates well with clinical alleviation of PBS/IC-related symptoms. In patients with persistent symptoms it may be painful and does not offer additional information. Thus, we do not recommend PST to be used as a routine clinical test in monitoring of PBS/IC treatment efficacy.     

Digital quantitative analysis of mast cell infiltration in interstitial cystitis

Aims

To evaluate the significance of mast cell infiltration in interstitial cystitis (IC) by comparison with equally inflamed controls using a digital quantification technique.

Methods

Bladder biopsy specimens from 31 patients with Hunner type IC and 38 patients with non‐Hunner type IC were analyzed. Bladder biopsy specimens from 37 patients without IC, including 19 non‐specific chronic cystitis (“non‐IC cystitis”) specimens and 18 non‐inflamed bladder (“normal bladder”) specimens, were used as controls. Mast cell tryptase‐, CD3‐, CD20‐, and CD138‐immunoreactive cells were quantified using digital image analysis software to evaluate both mast cell and lymphoplasmacytic cell densities. Mast cell and lymphoplasmacytic cell densities were counted independently in the entire lamina propria and detrusor areas and compared among the four groups.

Results

In the lamina propria, there were no significant differences in mast cell and lymphoplasmacytic cell densities between Hunner type IC and non‐IC cystitis or between non‐Hunner type IC and normal bladder specimens. In the detrusor, the mast cell densities were not significantly different among the four groups. Mast cell density was correlated with lymphoplasmacytic cell density, but not with clinical parameters.

Conclusions

Mast cell density is not significantly different between IC specimens and non‐IC control specimens with a similar degree of background inflammation. The intensity of mast cell infiltration generally correlated with that of lymphoplasmacytic cells. We conclude that mast cell count is of no value in the differential diagnosis between IC and other etiologies.     

Prevalence and incidence of interstitial cystitis in a managed care population

PURPOSE: We calculated the prevalence and incidence of physician diagnosed interstitial cystitis (IC) in men and women in a managed care population in the Pacific Northwest. MATERIALS AND METHODS: A computer search of the Kaiser Permanente Northwest (Portland, Oregon) database was performed for January 1998 to May 2002. The prevalence of IC in patients 25 to 80 years old was calculated using the 4 definitions of 1) patients assigned a diagnosis of IC, 2) patients assigned a diagnosis of IC without any of the consensus IC exclusion criteria, 3) patients who had also had undergone cystoscopy and 4) patients who had specifically undergone cystoscopy with hydrodistention for IC. A second database search was performed 1 year later (May 2003) to identify incident cases of IC. RESULTS: The prevalence of IC was 197 per 100,000 women and 41 per 100,000 men for definition 1, 158 per 100,000 women and 28 per 100,000 men for definition 2, 99 per 100,000 women and 19 per 100,000 men for definition 3, and 45 per 100,000 women and 8 per 100,000 men for definition 4. Using definition 2 the 1-year incidence of IC was 21 per 100,000 women and 4 per 100,000 men. The female-to-male ratio for each estimate was 5:1. CONCLUSIONS: The prevalence and incidence of interstitial cystitis is significantly higher for women and men than previously published estimates. Men account for a higher proportion of patients with IC than has previously been recognized.     

间质性膀胱炎发生前后膀胱组织组胺受体变化的动物实验研究

目的 探讨大鼠间质性膀胱炎发生前后膀胱组织中4种组胺受体(H1R、H2R、H3R和H4R)表达的变化. 方法体质量250～300 g的雌性SD大鼠30只,随机分为实验组(20只)和对照组(10只).实验组采用硫酸鱼精蛋白加氯化钾经尿道膀胱灌注建立间质性膀胱炎动物模型,2个月后处死,对照组直接处死.切取2组大鼠膀胱组织后行免疫组化染色,利用IPP 4.5图像分析软件计算各组组胺受体平均吸光度(-A)值,并进行统计学比较. 结果4种组胺受体主要表达于膀胱黏膜层,实验组H1R的(-A)值为0.054±0.031、H2R为0.032±0.021、H3R为0.047±0.033、H4R为0.149±0.191,对照组分别为0.017±0.011、0.018±0.015、0.014±0.011、0.060±0.039.实验组H1R、H2R和H3R的(-A)值明显高于对照组(P＜0.05),H4R的(-A) 值与对照组比较差异无统计学意义(P＞0.05). 结论H1R、H2R和H3R在间质性膀胱炎大鼠膀胱黏膜中表达显著升高,可能与间质性膀胱炎的发生相关,H3R可能是治疗间质性膀胱炎的新靶点.     

The ameliorating effect of melatonin on protamine sulfate induced bladder injury and its relationship to interstitial cystitis

PURPOSE: The pineal hormone melatonin was recently shown to have free radical scavenging ability and it reduces lipid peroxidation. In this morphological study we investigated the effects of melatonin on protamine sulfate (Sigma Chemical Co., St. Louis, Missouri) induced bladder injury. MATERIALS AND METHODS: Albino Wistar female rats were catheterized and intravesically infused with phosphate buffered solution (control group) or protamine sulfate (bladder injury group) dissolved in phosphate buffered solution. In the protamine sulfate plus melatonin group after protamine sulfate instillation melatonin was injected intraperitoneally. Bladder morphology was investigated by light and electron microscopy. Tissue samples were also obtained to determine bladder malondialdehyde levels. RESULTS: In the bladder injury group ulcerated areas, an irregular glycosaminoglycan layer, increased number of mast cells, vacuole formation, dilated perinuclear cistern, formation of pleomorphic and uniform microvilli, and dilated urothelial intercellular spaces were observed. In the bladder injury plus melatonin group a relatively normal urothelial topography, glycosaminoglycan layer and decreased number of mucosal mast cells, some dilatation between intercellular areas, less uniform microvilli and in most areas regular tight junctions were observed. CONCLUSIONS: Increased malondialdehyde levels as a result of protamine sulfate induction lead us to propose that free radicals may have a critical role in this injury. The significant decrease in malondialdehyde levels in the protamine sulfate plus melatonin group was in accordance with morphological findings. Thus, melatonin appears to exert a urothelial protective activity in a bladder injury model.     

Effects of l-arginine treatment on symptoms and bladder nitric oxide levels in patients with interstitial cystitis

Objectives. Nitric oxide (NO) is involved in host defense reactions, and NO production is elevated in various inflammatory disorders. We have found very high levels of luminal NO in the urinary bladder of patients with interstitial cystitis. Oral treatment with low doses of -arginine, the substrate for NO production, has been reported to alleviate symptoms in patients with interstitial cystitis. The aim of our investigation was to evaluate the effect of higher doses of -arginine in patients with interstitial cystitis and to study the effects of -arginine on NO production in the bladder.Methods. Nine women (age 69 ± 3 years) with interstitial cystitis were treated daily with 3 or 10 g of -arginine for 5 weeks. Symptoms were evaluated with an interstitial cystitis symptom score index, and NO production was measured. Patients with stress incontinence (n = 18) were used as control subjects for measurement of NO levels.Results. NO concentration in the urinary bladder was markedly elevated in the patients with interstitial cystitis (239 ± 60 ppb) compared with the control patients (15 ± 2 ppb). NO levels did not change in the patients with interstitial cystitis after oral treatment with -arginine (189 ± 72 ppb). There was no significant change in the symptom scores at either dose after 5 weeks of -arginine treatment.Conclusions. -arginine treatment in the doses used in this study did not change NO production in the urinary bladder in patients with interstitial cystitis. Furthermore, the patients in our study did not notice any relief of their symptoms.     

Cyto-injury factors in urine: a possible mechanism for the development of interstitial cystitis

PURPOSE: In most of our patients with interstitial cystitis (IC), the disease is associated with an increased urothelial permeability whose cause has not been identified. We postulate that both normal urine and the urine of IC patients contains factors capable of injuring the mucosa and causing an increased permeability that would allow urine components to leak into the bladder muscle. To test this hypothesis, we examined fractions of normal urine for toxic effects on bladder smooth muscle and epithelial cells in vitro. In the same in vitro system, we measured the effects of Tamm-Horsfall protein (THP), a normal urinary glycoprotein that may be a scavenger of injurious agents capable of "detoxifying" normal metabolic products. MATERIALS AND METHODS: Human urothelial cells (T24) and rabbit bladder smooth muscle cells were incubated overnight with various fractions prepared from healthy volunteers' urine. The urine fractions of molecular weights >100 Da were incubated overnight with either urothelial or smooth muscle target cells after no treatment or after heating to 56C, preincubation with THP, exposure to heparin, or elution from heparin. Cytotoxicity was determined for each group using a neutral red uptake assay. RESULTS: Urine fractions of molecular weight 500 to 1000 Da were cytotoxic to smooth muscle cells (39%) and urothelial cells (50%). Cytotoxicity levels for THP-treated fractions were significantly lower than those for untreated fractions in both urothelial cells (7% versus 89%, p <0. 001) and smooth muscle cells (8% versus 70%, p <0.01). Fractions exposed to heparin were less cytotoxic to smooth muscle cells (20%) than were untreated fractions (27%). Fractions eluted from heparin were also cytotoxic to urothelial cells (42%). CONCLUSIONS: Normal human urine contains heat labile, cationic components of low molecular weight that bind to heparin. These components, when separated from the bulk of the urinary wastes, are cytotoxic to urothelial cells as well as underlying smooth muscle cells, indicating their potential for causing bladder mucosal injury. The cytotoxic activity can be blocked by the presence of THP. This urinary cytoprotective activity of THP may play an important but unrecognized role in the development of IC.     

Toward a precise definition of interstitial cystitis: further evidence of differences in classic and nonulcer disease

PURPOSE: Interstitial cystitis is a bothersome condition in urological practice. There is continuous discussion on the extent and demarcation of this syndrome. Accumulated evidence indicates that interstitial cystitis is a heterogeneous syndrome. Today it is often divided into classic and nonulcer disease. Compared with classic interstitial cystitis the nonulcer type appears different in terms of demographic, endoscopic and histological findings as well as in the response to various types of treatment. However, in clinical series subdivision is not always performed, which makes it difficult to draw conclusions. We determined whether there are additional dissimilarities in clinical presentation in the 2 subtypes of interstitial cystitis. MATERIALS AND METHODS: We evaluated 130 patients with classic and 101 with nonulcer interstitial cystitis diagnosed according to National Institute for Diabetes and Digestive and Kidney Diseases criteria by surveying the clinical records, including voiding diaries. RESULTS: Patients with nonulcer disease were younger at diagnosis (p <0.0001) and at symptom onset. Furthermore, there was a marked and significant difference in bladder capacity while patients were under general anesthesia (p <0.0001). CONCLUSIONS: The current findings together with previous findings clearly demonstrate that the 2 subtypes of interstitial cystitis represent separate entities. We suggest refining the National Institutes of Health-National Institute for Diabetes and Digestive and Kidney Diseases criteria, so that subtyping scientific materials is considered mandatory, hence, ensuring that the 2 subtypes are evaluated separately in clinical studies.     

间质性膀胱炎大鼠动物模型膀胱黏膜保护前后组胺受体变化及意义

目的 探讨透明质酸膀胱灌注治疗间质性膀胱炎(IC)后膀胱组织中组胺受体变化的意义. 方法 IC模型大鼠20只,随机分为2组,每组10只.实验组尿道灌注0.8 g/L透明质酸.对照组即时处死.HE染色计数膀胱固有层单核炎症细胞,特殊染色计数肥大细胞.免疫组化染色2组大鼠膀胱组织,IPP4.5图像分析软件计算吸光度(A)值,比较2组间的差异. 结果 实验组单核炎症细胞数和肥大细胞数分别为(12.20±2.48)、(2.90±0.87)个/视野;组胺H1～H4受体A值分别为0.015±0.007、0.006±0.001、0.007±0.004、0.061±0.026;对照组单核炎症细胞数和肥大细胞数分别为(23.90±3.07)、(7.08±1.23)个/视野;组胺H1～H4受体A值分别为0.055±0.033、0.031±0.023、0.033±0.017、0.091±0.059.2组单核炎症细胞和肥大细胞数比较差异均有统计学意义(P＜0.01);H1、H2、H3受体A值明显减小(P＜0.05);组胺H4受体A值差异无统计学意义(P＞0.05). 结论 组胺H1、H2、H3受体参与IC发生,其受体拮抗剂可能用于临床治疗IC.     

Comparison of cystoscopic and histological findings in patients with suspected interstitial cystitis

PURPOSE: Although the exact etiology of interstitial cystitis remains elusive, bladder inflammation appears to be common in many patients. The National Institutes of Health (NIH) have established diagnostic criteria for interstitial cystitis based on the presence of irritative voiding symptoms in the absence of other identifiable pathology. Cystoscopic examination with hydrodistention performed in patients under anesthesia is part of the NIH diagnostic criteria. We determine if the severity of cystoscopic findings correlated with histological evidence of inflammation in patients with suspected interstitial cystitis. MATERIALS AND METHODS: A total of 69 patients who met NIH symptom criteria for interstitial cystitis and underwent cystoscopy, hydrodistention and bladder biopsy under anesthesia were reviewed. There were 2 investigators blinded to the histological data who independently reviewed operative reports. A urological pathologist blinded to the clinical data reviewed biopsies for inflammation severity. Cystoscopic and histological findings were then converted to a numeric scale. Numeric data were analyzed using the Pearson correlation coefficient. RESULTS: Cystoscopic examination revealed no evidence of interstitial cystitis in 6 patients (9%), mild changes in 27 (39%), moderate changes in 23 (33%) and severe changes in 13 (19%). Histological examination revealed no inflammation in 21 patients (30%), mild inflammation in 28 (41%), moderate inflammation in 11 (16%) and severe inflammation in 9 (13%). Histological scores correlated poorly with total and scaled cystoscopic severity scores (r = 0.295 and 0.349, respectively). CONCLUSIONS: Severity of cystoscopic findings observed during hydrodistention with anesthesia does not appear to correlate with the degree of inflammation identified histologically in patients with suspected interstitial cystitis.     

Stress and symptomatology in patients with interstitial cystitis: a laboratory stress model

PURPOSE: Although patients with interstitial cystitis frequently report symptom exacerbation due to stress, to our knowledge this association has not been empirically examined. We evaluated the effects of a laboratory mental stress challenge on symptoms of urgency and pain in patients with interstitial cystitis and healthy controls. MATERIALS AND METHODS: A total of 14 females with interstitial cystitis and 14 age matched controls participated in a laboratory session, including a 60-minute baseline measurement, 25 minutes of mental stress tasks and 75 minutes of recovery. Acute symptoms of pain and urgency were assessed at voiding 15 minutes before the stressor, and 25, 70 and 100 minutes after stressor onset. Chronic symptoms were evaluated by questions from the Interstitial Cystitis Data Base survey. RESULTS: Patients reported significantly greater pain and urgency than controls at all 4 voidings (p <0.005). Pain increased in patients from the prestressor point to 25 minutes after stressor onset (p <0.005), remained elevated at 70, and decreased between 70 and 100. At 100 minutes patient pain remained significantly elevated above baseline (p = 0.018). Patient urgency was significantly elevated over baseline by 70 minutes after stressor onset (p <0.001) and significantly decreased between 70 and 100 minutes (p <0.002). Controls had no symptom changes with stress. CONCLUSIONS: These findings indicate that an acute stressor evokes increased symptoms of pain and urgency in patients with interstitial cystitis but not in controls. Findings are consistent with sympathetic effects on inflammatory processes in interstitial cystitis. However, further evaluation of the mechanisms underlying stress related interstitial cystitis symptom exacerbation is needed to provide a more comprehensive understanding of these phenomena.     

Prevalence of interstitial cystitis symptoms in women: a population based study in the primary care office

PURPOSE: We estimated the prevalence of urinary symptoms related to interstitial cystitis (IC) in women in a primary care practice and confirmed in the United States the results of a Finnish population based prevalence study. MATERIALS AND METHODS: Every female patient presenting to our office for a routine office visit between January 9, 2004 and September 24, 2004 was evaluated for urinary symptoms using 2 validated surveys, namely the O'Leary-Sant (OLS) IC symptom and problem index, and the Pelvic Pain and Urgency/Frequency (PUF) patient symptom scale. RESULTS: Of the 1,218 women in the study group 13 (1.1%) reported severe symptoms and problems (12 or greater on the OLS survey), including 7 (0.6%) who met previously established criteria for probable IC. In the same population scores on the PUF questionnaire indicated that 154 women (12.6%) likely had IC. CONCLUSIONS: Based on previously published criteria for use of the OLS survey the prevalence of urinary symptoms corresponding to probable IC in our study population (575/100,000 or 0.57%, 95% CI 150 to 1,000) was similar to the 0.45% rate previously reported. However, the results of the PUF questionnaire indicated that the prevalence of IC in women may actually be much higher (12,600/100,000 or 12.6%, 95% CI 10,700 to 14,500). We suggest that the true prevalence of IC in women may be somewhere between these 2 extremes. Further investigation of these questionnaires as screening tools for IC is warranted. IC may be more common in women than previously reported.     

Depressive symptoms and quality of life in patients with interstitial cystitis

PURPOSE: Previous research suggests that patients with interstitial cystitis have poorer quality of life and higher levels of depressive symptoms. However, most studies to date have been limited by the lack of standard measures to describe the experience of living with interstitial cystitis. In addition, to our knowledge no study has used a structured interview to assess depressive symptomatology. We investigated the extent of depressive symptoms and impaired quality of life in a sample of female patients with interstitial cystitis compared with healthy controls. Relationships among physician rated symptom severity, quality of life and depressive symptoms were also examined. MATERIALS AND METHODS: At a clinic visit 65 female patients previously diagnosed with interstitial cystitis and 40 age matched, healthy controls completed questionnaires on depressive symptoms (Beck Depression Inventory) and quality of life (Medical Outcomes Study 36-Item Short Form), and a structured interview on depressive symptoms (Hamilton Rating Scale for Depression) with trained interviewers. RESULTS: Patients reported compromised quality of life compared with healthy controls across various domains, including physical functioning, ability to function in one's normal role and vitality. They also had more severe depressive symptoms on the 2 depression measures. In patients, greater interstitial cystitis severity was associated with greater compromise in physical and social functioning, and mental health but not in other quality of life domains or depressive symptoms. CONCLUSIONS: A diagnosis of interstitial cystitis is related to poorer functioning in various life domains. Decrements increase with disease severity.     

Prevalence of symptoms related to interstitial cystitis in women: a population based study in Finland

PURPOSE: Interstitial cystitis is a chronic inflammatory bladder disease. Despite intensive research its prevalence, etiology, diagnosis and appropriate treatment remain elusive. We estimated the prevalence of urinary symptoms related to interstitial cystitis in women in Finland. MATERIALS AND METHODS: We randomly selected 2,000 study participants 18 to 71 years old from the Finnish population register. The prevalence of urinary symptoms was evaluated using the validated O'Leary-Sant interstitial cystitis symptom and problem index questionnaire, which was mailed to subjects. Women with high (12 or greater) symptom and problem scores, including nocturia 2 or greater, pain 2 or greater, and excluding urinary infection and pregnancy, were considered most likely to have interstitial cystitis. RESULTS: The response rate after 2 mailings was 67.2% (1,343 respondents). After further exclusions 1,331 women (66.6%) comprised the final study group. Of these 1,331 respondents 11 (0.8%) reported severe symptoms and problems (12 or greater), including 6 (0.45%) who fulfilled the criteria for probable interstitial cystitis. CONCLUSIONS: The prevalence of urinary symptoms corresponding to probable interstitial cystitis is 450/100.000 (95% confidence interval 100 to 800), which is an order of magnitude higher than previously reported.     

Prevalence of clinically confirmed interstitial cystitis in women: a population based study in Finland

PURPOSE: Interstitial cystitis (IC) is a clinical condition occurring predominantly in women that is characterized by irritative voiding symptoms, including urinary frequency, urgency and pain. To our knowledge its etiology is unknown and little is known about its occurrence. We evaluated the prevalence of IC in women in Finland. MATERIALS AND METHODS: A total of 2,000 participants were randomly selected from the Finnish population register. Urinary symptoms were evaluated using the validated O'Leary-Sant IC symptom and problem index questionnaire. Women with moderate or severe symptom scores (7 or higher) without any urinary tract infection during the last month were invited to undergo clinical examination. RESULTS: Of the 1,331 respondents 32 had moderate or severe symptoms involving a suspicion of IC, of whom 21 underwent clinical evaluation. Three women were found to have probable IC and 4 had possible IC. Thus, the prevalence of clinically confirmed probable IC in women was 230/100.000 (95% CI 100 to 360) and that of possible/probable IC was 530/100.000 (95% CI 140 to 910). Considering the lack of information on 8 patients with urinary symptoms the corrected estimates were 300/100,000 (95% CI 120 to 770) and 680/100,000 women (95% CI 360 to 1,300), respectively. CONCLUSIONS: Our results based on a large and representative population, and clinically confirmed diagnoses indicate that IC is substantially more common than previously thought.     

Recruitment, distribution and phenotypes of mast cells in interstitial cystitis

PURPOSE: Interstitial cystitis (IC) is a chronic disabling condition of unknown etiology. One of its major characteristics is an increase in mast cells (MC) showing signs of activation. It has been suggested that the proteinase content defines two MC types: MC(TC), containing chymase and tryptase, and MC(T), which contains tryptase but lacks chymase. Here, we investigated the MC distribution and the MC proteinase expression in IC together with the tissue expression of the major MC growth factors, stem cell factor (SCF) and interleukin-6 (IL-6). MATERIALS AND METHODS: MC were enumerated in bladder specimens from patients with classic IC, nonulcer IC and controls. MC were visualized in terms of metachromasia, reflecting glycosaminoglycan content, and immunohistochemically, visualizing tryptase, chymase and IL-6 as well as the surface markers CD117 and SCF. RESULTS: Classic IC displayed a 6 to 10-fold increase of MC identified by proteinase content while in nonulcer IC there were twice as many MC as in controls. In contrast to nonulcer IC and controls, classic IC displayed an abundance of epithelial MC. Fewer CD117+ than proteinase+ MC were detected in IC but not in controls. Classic IC coexpressed SCF and IL-6 in the epithelium and displayed numerous SCF and IL-6+ cells in the mucosa and detrusor muscle, many of which were MC. CONCLUSIONS: Redistribution of MC into the epithelium and a high bladder wall MC density distinguish classic IC from nonulcer IC. Our findings suggest an SCF/IL-6-driven MC response in IC. They also indicate a downregulation of the SCF receptor in IC.