scholarly journals LOCAL IMMUNE RESPONSE IN PATIENTS WITH CLASSIC AND NON-ULCER TYPE OF INTERSTITIAL CYSTITIS / BLADDER PAIN SYNDROME

2021 ◽  
Author(s):  
R. F. Sholan
Keyword(s):  
Mast Cells ◽  
Interstitial Cystitis ◽  
Plasma Cells ◽  
Bladder Wall ◽  
Pain Syndrome ◽  
Bladder Pain Syndrome ◽  
Bladder Pain ◽  
Group I ◽  
Tnf Α ◽  
Group Ii

Several hypotheses regarding the pathophysiology of interstitial cystitis / bladder pain syndrome (IC / BPS) have been put forward, but no consensus has yet been reached. It is suggested that cytokines are involved in IC / BPS, as well as in inflammatory autoimmune diseases. Examining various biomarkers of bladder tissue, including mast cells is underway. However, few reports on a consistent immune activity profile are available. The aim of the study was to assess the cytokine profile, counts of mast cells and plasma cells as well as their relationship in patients with IC / BPS with and without Hunner's lesions. 44 women with Hunner's lesions of IC / BPS (group I) and 82 women with non-ulcer type (group II) were examined. Patients were questioned on the Pelvic Pain Symptom Scale, Urinary Frequency Scale (PUF), Visual Analogue Scale (VAS) and O'Leary-Santa Interstitial Cystitis Symptom Index (ICSI). Cystoscopy and hydrodistension of the bladder were performed under general anesthesia. In biopsies of the bladder wall, the number of plasma cells and mast cells was assessed, in urine - IL-1β, IL-6, IL-8, TNF-α. Statistical processing of the results was carried out using the Statistica software for Microsoft Excel release 6 (StatSoft, USA). The Student's t-test, Spearman's correlation coefficient were calculated. In patients with the Hunner type of IC / BPS, there was an insignificant increase in the scale indices and decreased magnitude for average volume, urination frequency, and maximum emptying volume. The maximum bladder capacity during hydrodistension was lowered by 42.01% (p <0.001). The level of IL-8 in group I was higher on average by 28.57% (p = 0.434) as compared with that in group II, IL-6 - by 13.46% (p = 0.638), TNF-α - by 9.09% (p = 0.244) and IL-1β – by 4.13% (p = 0.859). The number of mast cells in patients of group I vs. group II was higher by 40.65% (p <0.05). In group I, a marked relationship was found between count of mast cells and plasma cells (r = -0.555, p> 0.05), as well as between count of plasma cells and IL-6 level (r = -0.639, p <0.05). In group II, a significant connection was found between count of mast cells and TNF-α level (r = +0.562, p <0.05). Patients with Hunner's IC / BPS are characterized by severe inflammation, wherein mast cells are involved in induction. Determination of cytokines in urine can provide a non-invasive division of IC / BPS into ulcerative and non-ulcerative groups.

scholarly journals Immune Cell Profiles and Cytokine Levels of Patients with Interstitial Cystitis/Bladder Pain Syndrome

2020 ◽  
Author(s):  
Robert M. Moldwin ◽  
Vishaan Nursey ◽  
Oksana Yaskiv ◽  
Siddhartha Dalvi ◽  
Michael Funaro ◽  
...  
Keyword(s):  
Interstitial Cystitis ◽  
Plasma Cells ◽  
Immune Cell ◽  
Pain Syndrome ◽  
Fold Increase ◽  
Bladder Pain Syndrome ◽  
Bladder Tissue ◽  
Bladder Pain ◽  
Tnf Α ◽  
Significant Difference

AbstractAimsTo quantify the number of immune cells in the bladder urothelium and concentrations of urinary cytokines in patients with Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS). To identify differences in these measures in IC/BPS patients with Hunner’s lesions (IC/BPS-HL) and without Hunner’s lesions (IC/BPS-NHL).MethodsBladder tissue biopsies were obtained from 48 patients with IC/BPS-HL and unaffected controls (UC) and stained with antibodies for various immune cell markers such as CD138, CD20 and CD56. Levels of cytokines (Interferon (IFN)-γ, Interleukin (IL)-1β, IL-2, IL- 4, IL-6, IL-8, IL12P70, IL-13, and TNF-α) were measured from normalized urine obtained from 18 IC/BPS-HL, 18 IC/BPS-NHL, and 4 UC.ResultsNumbers of CD138+ plasma cells, CD20+ B cells, and CD3+ T cells were significantly increased (50 fold, 30 fold, and an almost 3 fold increase, respectively; p-values: 1.34E-06, 3.26E-04, and 2.52E-6) in the bladders of IC/BPS-HL patients compared to UC. Patients with IC/BPS-HL had significantly elevated urinary levels of IL-6 (p=0.0028) and TNF-α (p=0.009) compared to patients with IC/BPS-NHL and UC. In contrast, IL-12p70 levels were significantly higher in the patients with IC/BPS-NHL than in HL patients (p=0.033). No significant difference in IL-12p70 levels were observed between IC/BPS-HL and UC.ConclusionDifferent cytokines were elevated in the urine of IC/BPS patients with and without HL, suggesting differences in underlying disease processes. Elevated levels of CD138+, CD20+, and CD3+ cells in HL indicate B and T-cell involvement in lesion formation. Determining which cytokines and immunological pathways are present in IC/BPS-HL could elucidate the disease mechanism.

scholarly journals Relationships between urinary neural and immune factors in the patients with interstitial cystitis/ bladder painful syndrome

2020 ◽  
Vol 22 (5) ◽  
pp. 879-886
Author(s):  
R. F. Sholan
Keyword(s):  
Mast Cells ◽  
Interstitial Cystitis ◽  
Pearson Correlation ◽  
Control Level ◽  
Clinical Manifestations ◽  
Control Group ◽  
Bladder Tissue ◽  
Bladder Pain ◽  
Group I ◽  
Group Ii

The purpose of this work was to study the relationships between urinary cytokines, mast cells and nerve growth factor (NGF) in the patients with interstitial cystitis/bladder pain syndrome (IC/BPS). Sixty-eight women with clinically diagnosed IC/BPS were under study. Their mean age was 54.2±12.4 years. Urinary concentrations of interleukins (IL-1β, IL-6, IL-8), tumor necrosis factor-α (TNFα), and NGF were determined by ELISA technique. Mast cells were identified in biopsies of mucous membranes from urinary bladder harvested during cystoscopy. Statistical evaluation was performed by Statistica program in Microsoft Excel. Pearson correlation quotients were calculated. Depending on the type of IC/BPS, the patients were divided into 2 groups: group I included 36 patients with classic type of disease; group II comprised 32 patients with non-ulcer type of IC/BPS. No significant differences were revealed between the groups. In 13.9% of patients from group I, the onset of clinical manifestations of the disease was observed at the age of less than 40 years; in group II, 28.1% of the examined mentioned appearance of the disease symptoms at this age. The levels of IL-1β in the patients from group I was 2.4 times higher than in controls (p < 0.05). IL-6, IL-8 and TNFα concentrations exceeded control values by 2.0 (p < 0.05), 2.5 (p < 0.05) and 2.0 times (p < 0.05), respectively. In the patients from group II, the content of IL-1β, IL-6, IL-8 and TNFα was 2.4 (p < 0.05), 2.0 (p < 0.05), 2.0 (p < 0.05) and 1.9 (p < 0.05) times higher than in the control group, respectively. There were no significant differences between groups I and II, in IL-1β, IL-6, and TNFα levels, except of IL-8 in women of group I that was 20.3% higher than in group II. The urinary NGF level in the patients with IC/BPS exceeded the control level 1.6 times (p < 0.05) for group I, and 1.5 times (p < 0.05) for group II. The number of mast cells in the patients of group I was significantly higher than in controls and in group II, i.e., 1.6 (p < 0.05) and 1.4 times (p < 0.05), respectively. In most cases, a direct weak correlation was revealed between the indices. Only in group I, a moderate correlation (r = + 0.508) could be detected between IL-1β and mast cells. Determination of cytokine levels allows to detect activation of inflammatory cells in bladder tissue and provides an opportunity for developing diagnostic strategies. Increased numbers of mast cells may indicate the importance of these cells in the disease progression, whereas elevated levels of NGF in urine suggests that IC/BPS may be caused by chronic inflammation.

scholarly journals THE EFFECTIVENESS OF TNF-Α INHIBITOR THERAPY IN BLADDER PAIN SYNDROME/INTERSTITIAL CYSTITIS PATIENTS: A SYSTEMATIC REVIEW AND META-ANALYSIS

2021 ◽  
Vol 28 (2) ◽  
pp. 194-201
Author(s):  
Ahmad Kholis ◽  
Soetojo ◽  
Wahjoe Djatisoesanto
Keyword(s):  
Systematic Review ◽  
Interstitial Cystitis ◽  
Meta Analysis ◽  
Pain Syndrome ◽  
Response Assessment ◽  
Bladder Pain Syndrome ◽  
Inhibitor Therapy ◽  
Global Response ◽  
Bladder Pain ◽  
Tnf Α

Objective: To evaluate the effectiveness of TNF-α inhibitor therapy in Bladder Pain Syndrome/Interstitial Cystitis (BPS/IC) patients compared to placebo, assessed using Global Response Assessment (GRA). Material & Methods: A systematic review and meta-analysis. Subjects were patients with moderate to severe diagnosis of BPS/IC who were given TNF-α inhibitor versus placebo, with the Global Response Assessment (GRA) (patient-reported self-reported BPS/IC treatment response scale). A systematic literature search was carried out on the English databases PubMed/MEDLINE and Science  Direct, published until September 2020. Data were extracted independently and assessed the bias and quality of each selected article. Results: Initially there were 124 studies. After further selection, 2 RCT studies were included in the criteria for this study. The number of samples obtained was 85 patients. There is 1 study that used 400 mg of certolizumab pegol subcutaneously and 1 study used adalimumab 80 mg subcutaneously and followed by 40 mg subcutaneously for 2 weeks. Both studies had statistically low heterogeneity with I2 = 0% (P = 0.34), so fixed effect statistical model was used to determine the result. Furthermore, there was no significant difference (P = 0.32) between the number of GRA responders from the TNF-α inhibitor and placebo therapy groups, with odds ratio of 1.61 (CI = 0.65-4.00). Conclusion: TNF-α inhibitor therapy did not increase GRA responders when compared to placebo.

scholarly journals Houttuynia cordata Extract Ameliorates Bladder Damage and Improves Bladder Symptoms via Anti-Inflammatory Effect in Rats with Interstitial Cystitis

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Wenbiao Li ◽  
Fei Yang ◽  
Hailun Zhan ◽  
Bolong Liu ◽  
Jiarong Cai ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Interstitial Cystitis ◽  
Intraperitoneal Injection ◽  
Sham Group ◽  
Pain Syndrome ◽  
Bladder Pain Syndrome ◽  
Bladder Pain ◽  
Houttuynia Cordata ◽  
Bladder Weight

The mechanism of interstitial cystitis/bladder pain syndrome (IC/BPS) remains unclear to date, but reports showed that bladder inflammation and increasing number of activating mast cells in bladder tissues were common in patients with IC/BPS. Houttuynia cordata is widely used in Chinese traditional medicine, and its function of anti-inflammation has been proved. The purpose of this study was to investigate the efficacy and possible mechanisms of the Houttuynia cordata (HC) extract in the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS). In the current study, a total of 30 adult female rats were randomly divided into three groups: sham group (n = 10), cyclophosphamide + saline (CYP + NS) group (n = 10), and cyclophosphamide + Houttuynia cordata extract (CYP + HC) group (n = 10). The animal model of IC/BPS was induced with cyclophosphamide (75 mg/kg, intraperitoneal injection, once every 3 days for 10 days) in the CYP + NS group and CYP + HC group, and sham rats received a volume-matched injection of saline. After anesthesia with urethane (0.8 g/kg, intraperitoneal injection), intravesical administration of either saline (1 ml) or Houttuynia cordata extract (1 ml, 2 g/ml) was continued once per day for a week in the CYP + NS group and CYP + HC group, respectively. Subsequently, urinary frequency, nociceptive behaviors, cystometry, bladder weight, histological changes, and cytokine (IL-6, IL-8, TNF-α) concentration were evaluated and compared among the three groups. Variables including inflammatory grade, mast cell number, proportion of activated mast cells, bladder weight, cytokine concentration of bladder homogenates, and frequency of urination significantly increased in the CYP + NS group compared with the sham group (P<0.01) and CYP + HC group (P<0.01). Besides, compared with the CYP + NS group, longer intercontraction interval, bigger bladder capacity, higher nociceptive threshold, fewer number of mast cells, and lower proportion of activated mast cells were found in the CYP + HC group (P<0.01). Our study demonstrated that the Houttuynia cordata extract can effectively inhibit mast cell proliferation and activation and downregulate proinflammatory cytokine in a rat model of IC/BPS induced with cyclophosphamide and might be potentially valuable for the treatment of IC/BPS.

scholarly journals Dysregulation of bladder corticotropin-releasing hormone receptor in the pathogenesis of human interstitial cystitis/bladder pain syndrome

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Jia-Fong Jhang ◽  
Lori A. Birder ◽  
Yuan-Hong Jiang ◽  
Yung-Hsiang Hsu ◽  
Han-Chen Ho ◽  
...  
Keyword(s):  
Interstitial Cystitis ◽  
Hormone Receptor ◽  
Bladder Wall ◽  
Pain Syndrome ◽  
Bladder Pain Syndrome ◽  
Corticotropin Releasing Hormone ◽  
Bladder Pain ◽  
Releasing Hormone ◽  
Control Subjects ◽  
And Control

AbstractStress is associated with exacerbated symptoms in patients with interstitial cystitis/bladder pain syndrome (IC/BPS). To investigate the mechanism of stress implicated on IC/BPS, we investigated expression of stress-response receptor corticotropin-releasing hormone receptor (CRHR) in bladder from IC/BPS patients. Twenty-three IC/BPS patients with Hunner’s lesion (HIC), 51 IC/BPS patients without Hunner’s lesion (NHIC), and 24 patients with stress urinary incontinence as controls were enrolled. Cystoscopic biopsies of bladder wall including mucosa and submucosa were obtained from all patients. Western blotting was used to investigate the bladder expression of the CRHR1 and CRHR2. Immunochemical staining revealed CRHR1 expression was mainly located in the submucosa while CRHR2 expression was mainly in uroepithelial cells. Compared to control subjects, the CRHR1 expression was significantly higher, while CRHR2 expression was significantly lower in IC/BPS patients. Further analysis of patients with HIC, NHIC, and control subjects showed that bladder in patients with HIC had significantly higher expressions of CRHR1 and significantly lower CRHR2. CRHR2 expression was significantly negatively correlated with O’Leary-Sant score and bladder pain. Our results indicate dysregulation of bladder CRHR1 and CRHR2 in patients with IC/BPS, and suggest CRH signaling may be associated with IC/BPS symptoms.

Clinical and histological findings in bladder pain syndrome/interstitial cystitis: The implication of time of symptoms

2018 ◽  
Vol 11 (4) ◽  
pp. 248-253
Author(s):  
Daniele Porru ◽  
Valentina Bobbi ◽  
Carmelo Di Franco ◽  
Alessandra Viglio ◽  
Mattia Novario ◽  
...  
Keyword(s):  
Interstitial Cystitis ◽  
Symptom Onset ◽  
Bladder Wall ◽  
Pain Syndrome ◽  
Bladder Pain Syndrome ◽  
Detrusor Muscle ◽  
Level Of Evidence ◽  
Bladder Pain ◽  
Bladder Biopsy ◽  
The Impact

Objective: To find out whether a correlation exists between denudation of urothelium and time of symptom onset in patients with bladder pain syndrome/interstitial cystitis (BPS/IC), and to search for a correlation between the impact of symptoms. Patients and methods: Fifty-seven consecutive patients underwent cystoscopy under anaesthesia to classify those cases suspected of being affected with BPS/IC. The time elapsed between onset of symptoms and diagnosis at the time of bladder biopsy was also defined as BPS/IC duration. Bladder biopsies were taken including detrusor muscle, three deep cold biopsies of posterior, anterior and lateral bladder wall. Results: Statistical analysis showed significant correlation between BPS/IC duration and the presence of Hunner’s lesions ( P<0.023). Hunner’s lesion with cystoscopy and histological evidence of urothelial denudation with bladder biopsy appear to be related to BPS/IC duration. Thus an early diagnosis allows an appropriate therapeutic approach to be started to prevent a more severe evolution of this multifaceted painful syndrome. Conclusions: Our study shows a correlation between the time of symptom onset and evidence of urothelial denudation and with detrusor mast cell count in the whole group of patients. BPS/IC duration did not seem to correlate with the severity of symptoms, but rather with the presence of associated diseases. Level of evidence: Not applicable for this multicentre audit.

scholarly journals Notch1 Signaling Contributes to Mechanical Allodynia Associated with Cyclophosphamide-Induced Cystitis by Promoting Microglia Activation and Neuroinflammation

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Jialiang Chen ◽  
Honglu Ding ◽  
Bolong Liu ◽  
Xiangfu Zhou ◽  
Xin Zhou ◽  
...  
Keyword(s):  
Interstitial Cystitis ◽  
Mechanical Allodynia ◽  
Pain Syndrome ◽  
Bladder Pain Syndrome ◽  
Microglia Activation ◽  
Bladder Pain ◽  
Withdrawal Threshold ◽  
Notch1 Signaling ◽  
Tnf Α ◽  
The Impact

Aims. Notch1 signaling regulates microglia activation, which promotes neuroinflammation. Neuroinflammation plays an essential role in various kinds of pain sensation, including bladder-related pain in bladder pain syndrome/interstitial cystitis (BPS/IC). However, the impact of Notch1 signaling on mechanical allodynia in cyclophosphamide- (CYP-) induced cystitis is unclear. This study is aimed at determining whether and how Notch1 signaling modulates mechanical allodynia of CYP-induced cystitis. Methods. CYP was peritoneally injected to establish a bladder pain syndrome/interstitial cystitis (BPS/IC) rat model. A γ-secretase inhibitor, DAPT, was intrathecally injected to modulate Notch1 signaling indirectly. Mechanical withdrawal threshold in the lower abdomen was measured with von Frey filaments using the up-down method. The expression of Notch1 signaling, Iba-1, OX-42, TNF-α, and IL-1β in the L6-S1 spinal dorsal horn (SDH) was measured with Western blotting analysis and immunofluorescence staining. Results. Notch1 and Notch intracellular domain (NICD) were both upregulated in the SDH of the cystitis group. Moreover, the expression of Notch1 and NICD was negatively correlated with the mechanical withdrawal threshold of the cystitis rats. Furthermore, treatment with DAPT attenuated mechanical allodynia in CYP-induced cystitis and inhibited microglia activation, leading to decreased production of TNF-α and IL-1β. Conclusion. Notch1 signaling contributes to mechanical allodynia associated with CYP-induced cystitis by promoting microglia activation and neuroinflammation. Our study showed that inhibition of Notch1 signaling might have therapeutic value for treating pain symptoms in BPS/IC.

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