Inflammatory Urinary Cytokine Expression and Quality of Life in Patients With Overactive Bladder

Pillalamarri, Nirmala; Shalom, Dara F.; Pilkinton, Marjorie L.; Winkler, Harvey A.; Chatterjee, Prodyot K.; Solanki, Malvika H.; Metz, Christine N.

doi:10.1097/spv.0000000000000492

Cited by 13 publications

(14 citation statements)

References 31 publications

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“…Previous studies of urinary IL-10 have shown variable results; some studies report increased IL-10 in OAB [2], and also in elderly patients with asymptomatic bacteriuria [9], while others report decreased IL-10 in OAB [39]. The only other well-described anti-inflammatory cytokine in our study was IL-4, which has previously been shown to be decreased [5] or unchanged [39] in OAB patients. However, in animal UTI PLOS ONE models, IL-4 appears to protect against bladder inflammation [5].…”

Section: Plos Onecontrasting

confidence: 60%

“…CXCL10 is chemotactic for macrophages and thus enhances the innate immune response to infection, and is part of the inflammatory response to injury. Increased levels of CXCL10 have previously been reported in women with UTI [3] but not in women with urge incontinence [3,39]. These findings highlight the role of the innate immune system in the bladder response to bacteriuria.…”

Section: Plos Onementioning

confidence: 63%

“…IL-10 typically inhibits the release of inflammatory cytokines in response to bacterial lipopolysaccharide [45]. Previous studies of urinary IL-10 have shown variable results; some studies report increased IL-10 in OAB [2], and also in elderly patients with asymptomatic bacteriuria [9], while others report decreased IL-10 in OAB [39]. The only other well-described anti-inflammatory cytokine in our study was IL-4, which has previously been shown to be decreased [5] or unchanged [39] in OAB patients.…”

Section: Plos Onementioning

confidence: 99%

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Urinary cytokines in women with refractory detrusor overactivity: A longitudinal study of rotating antibiotic versus placebo treatment

et al. 2021

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Over 50% of women with detrusor overactivity (DO), who do not respond to therapy have been shown to have bacteriuria, which may stimulate the release of inflammatory cytokines than can enhance nerve signalling, leading to symptoms of urgency. This study made use of a consecutive series of urine samples collected from women with refractory DO, who participated in a clinical trial of rotating antibiotic therapy. The aim was to determine the effect of bacteriuria and antibiotic treatment on the levels of urinary cytokines, and to correlate the cytokine concentration with patient outcome measures relating to urgency or urge incontinence. The urinary cytokines chosen were IL-1α, IL-1 receptor antagonist, IL-4, IL-6, IL-8, IL-10, CXCL10 (IP-10), MCP-1 and TNF-α. The presence of bacteriuria stimulated a significant increase in the concentrations of IL-1α (P 0.0216), IL-1 receptor antagonist (P 0.0264), IL-6 (P 0.0003), IL-8 (P 0.0043) and CXCL-10 (P 0.009). Antibiotic treatment significantly attenuated the release of IL-1α (P 0.005), IL-6 (P 0.0027), IL-8 (P 0.0001), IL-10 (P 0.049), and CXCL-10 (P 0.042), i.e. the response to the presence of bacteria was less in the antibiotic treated patients. Across the 26 weeks of the trial, antibiotic treatment reduced the concentration of five of the nine cytokines measured (IL-1α, IL-6, IL-8, IL-10 and CXCL-10); this did not reach significance at every time point. In antibiotic treated patients, the urinary concentration of CXCL-10 correlated positively with four of the six measures of urgency. This study has shown that cytokines associated with activation of the innate immune system (e.g. cytokines chemotactic for or activators of macrophages and neutrophils) are reduced by antibiotic therapy in women with refractory DO. Antibiotic therapy is also associated with symptom improvement in these women, therefore the inflammatory response may have a role in the aetiology of refractory DO.

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Section: Plos Onecontrasting

confidence: 60%

Section: Plos Onementioning

confidence: 63%

Section: Plos Onementioning

confidence: 99%

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Urinary cytokines in women with refractory detrusor overactivity: A longitudinal study of rotating antibiotic versus placebo treatment

et al. 2021

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“…As for the cytokines, we confirmed that the injection of CYP significantly increases IL-1β, IL-6, and TNF-α levels in the urinary bladder of animals, whereas it reduces the values of the anti-inflammatory IL-10. Comparable changes in the bladder levels of IL-1β, IL-6, IL-10, and TNF-α are associated with detrusor overactivity, 20 and at least partially, with interstitial cystitis/painful bladder syndrome. 21 Ague et al 12 also reported the enhanced tissue levels of IL-1β and IL-6 (along with the unchanged tissue levels of IL-10) following CYP administration.…”

Section: Discussionmentioning

confidence: 99%

Intravesical administration of blebbistatin prevents cyclophosphamide‐induced toxicity of the urinary bladder in female Wistar rats

Wróbel

Serefko

Bańczerowska‐Górska

et al. 2019

Neurourology and Urodynamics

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Aims The main goal of our study was to investigate whether blebbistatin would prevent the cyclophosphamide (CYP)‐induced changes in cystometric and inflammatory parameters indicating the development of bladder inflammation and bladder overactivity. As the nature of CYP‐induced urotoxicity is inflammatory, we assume that agents presenting an anti‐inflammatory potential, such as blebbistatin, are worth special attention. Materials and Methods The experiments were carried out in female Wistar rats. Surgical procedures, cystometric investigations, measurements of bladder edema and urothelium thickness as well as biochemical analyses were performed according to the published literature. Results As expected, an acute administration of CYP (200 mg/kg, intraperitoneally) induced changes in the cystometric parameters and the levels of the tested biomarkers (ie, interleukin 1‐β, interleukin 6, interleukin 10, tumor necrosis factor‐α, nerve growth factor, brain‐derived neurotrophic factor, heparin‐binding epidermal growth factor‐like growth factor, insulin‐like growth factor‐binding protein 3, C‐X‐C motif chemokine 10, orosomucoid‐1, Tamm‐Horsfall protein, hemopexin, and occludin), indicating the development of bladder overactivity and bladder inflammation, respectively. These changes were accompanied by bladder edema and increased urothelium thickness. Intravesical infusion of blebbistatin for 7 days (125 nmol/day) prevented all symptoms of the CYP‐induced urotoxicity. Conclusions Blebbistatin might be a promising novel agent for the treatment of bladder dysfunctions, like CYP‐induced hemorrhage cystitis or bladder overactivity, since it diminished the increased urinary bladder levels of proinflammatory markers and normalized the concentrations of the anti‐inflammatory ones. This effect was accompanied by amelioration of bladder edema and permeability, and normalization of both urothelium thickness and values of the cystometric parameters.

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“…Furuta et al ( 2018 ) have recently demonstrated increased expression of multiple chemokine markers in urine of IC patients with and without Hunner’s ulcer compared to OAB patients. OAB also has an elusive etiology but an inflammatory contribution has also been suggested (Steers, 2000 ; Compérat et al, 2006 ; Pillalamarri et al, 2017 ). Tyagi et al ( 2012 ) detected an increase (10-fold) in the chemokine, CCL2, in the urine of OAB patients vs. controls.…”

Section: Introductionmentioning

confidence: 99%

Expression and Function of Chemokines CXCL9-11 in Micturition Pathways in Cyclophosphamide (CYP)-Induced Cystitis and Somatic Sensitivity in Mice

Guo

Chang

Hauke

et al. 2018

Front. Syst. Neurosci.

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Changes in urinary bladder function and somatic sensation may be mediated, in part, by inflammatory changes in the urinary bladder including the expression of chemokines. Male and female C57BL/6 mice were treated with cyclophosphamide (CYP; 75 mg/kg, 200 mg/kg, i.p.) to induce bladder inflammation (4 h, 48 h, chronic). We characterized the expression of CXC chemokines (CXCL9, CXCL10 and CXCL11) in the urinary bladder and determined the effects of blockade of their common receptor, CXCR3, at the level urinary bladder on bladder function and somatic (hindpaw and pelvic) sensation. qRT-PCR and Enzyme-Linked Immunoassays (ELISAs) were used to determine mRNA and protein expression of CXCL9, CXCL10 and CXCL11 in urothelium and detrusor. In urothelium of female mice treated with CYP, CXCL9 and CXCL10 mRNA significantly (p ≤ 0.01) increased with CYP treatment whereas CXC mRNA expression in the detrusor exhibited both increases and decreases in expression with CYP treatment. CXC mRNA expression urothelium and detrusor of male mice was more variable with both significant (p ≤ 0.01) increases and decreases in expression depending on the specific CXC chemokine and CYP treatment. CXCL9 and CXCL10 protein expression was significantly (p ≤ 0.01) increased in the urinary bladder with 4 h CYP treatment in female mice whereas CXC protein expression in the urinary bladder of male mice did not exhibit an overall change in expression. CXCR3 blockade with intravesical instillation of AMG487 (5 mg/kg) significantly (p ≤ 0.01) increased bladder capacity, reduced voiding frequency and reduced non-voiding contractions in female mice treated with CYP (4 h, 48 h). CXCR3 blockade also reduced (p ≤ 0.01) hindpaw and pelvic sensitivity in female mice treated with CYP (4 h, 48 h). CXC chemokines may be novel targets for treating urinary bladder dysfunction and somatic sensitization resulting from urinary bladder inflammation.

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Inflammatory Urinary Cytokine Expression and Quality of Life in Patients With Overactive Bladder

Cited by 13 publications

References 31 publications

Urinary cytokines in women with refractory detrusor overactivity: A longitudinal study of rotating antibiotic versus placebo treatment

Urinary cytokines in women with refractory detrusor overactivity: A longitudinal study of rotating antibiotic versus placebo treatment

Intravesical administration of blebbistatin prevents cyclophosphamide‐induced toxicity of the urinary bladder in female Wistar rats

Expression and Function of Chemokines CXCL9-11 in Micturition Pathways in Cyclophosphamide (CYP)-Induced Cystitis and Somatic Sensitivity in Mice

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