Elevated Urine Levels of Macrophage Migration Inhibitory Factor in Inflammatory Bladder Conditions: A Potential Biomarker for a Subgroup of Interstitial Cystitis/Bladder Pain Syndrome Patients

Vera, Pedro L.; Preston, David; Moldwin, Robert; Erickson, Deborah; Mowlazadeh, Behzad; Ma, Fei; Kouzoukas, Dimitrios E.; Meyer-Siegler, Katherine L.; Fall, Magnus

doi:10.1016/j.urology.2018.02.039

Cited by 28 publications

(18 citation statements)

References 29 publications

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“…Glycyrrhizin is widely available as a nutritional supplement whereas MIF inhibitors are currently undergoing clinical testing for several inflammatory conditions . Our recent report of urine MIF elevation in IC patients with Hunner's lesions further supports a potential role for MIF in IC/BPS and warrants further investigation . Therefore, MIF and HMGB1 represent novel targets for treating bladder pain and might provide a therapeutic avenue for the treatment of IC/BPS.…”

Section: Discussionsupporting

confidence: 64%

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Protease activated‐receptor 4 activation as a model of persistent bladder pain: Essential role of macrophage migration inhibitory factor and high mobility group box 1

Hunt

Leng

et al. 2018

Int J of Urology

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Section: Discussionsupporting

confidence: 64%

“…26 Our recent report of urine MIF elevation in IC patients with Hunner's lesions further supports a potential role for MIF in IC/BPS and warrants further investigation. 27 Therefore, MIF and HMGB1 represent novel targets for treating bladder pain and might provide a therapeutic avenue for the treatment of IC/BPS.…”

Section: Discussionmentioning

confidence: 99%

Protease activated‐receptor 4 activation as a model of persistent bladder pain: Essential role of macrophage migration inhibitory factor and high mobility group box 1

Hunt

Leng

et al. 2018

Int J of Urology

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“…Urinary MIF was increased in HIC patients (43) while levels in NHL IC patients (55) were similar to controls (100). In males, bacterial cystitis (50 patients) and radiation cystitis (18 patients), MIF levels were similar to female HIC patients as opposed to controls (119 male patients) . MIF is a non‐invasive urine biomarker with a potential to identify patients with bladder inflammation.…”

Section: Resultsmentioning

confidence: 95%

“…NO evaporation from the bladder appears to be a definitive marker in distinguishing HLs from the NHL category . Macrophage MIF, urinary proinflammatory gene expression, CXCL, NGF have been found to be elevated in HL disease …”

Section: Introductionmentioning

confidence: 90%

“…37,38 Macrophage MIF, urinary proinflammatory gene expression, CXCL, NGF have been found to be elevated in HL disease. [39][40][41] Treatment of HLs includes TUR, electrocoagulation/fulguration, laser ablation, and corticosteroid injection, [42][43][44][45][46][47][48] providing good to excellent clinical results, however applicable in HL disease only. Cyclosporine A has been effective in treating HL IC/BPS with more limited efficacy in NHL.…”

Section: Introductionmentioning

confidence: 99%

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Hunner lesion versus non‐Hunner lesion interstitial cystitis/bladder pain syndrome

et al. 2019

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Background Global consensus on the standardization of terminology for interstitial cystitis/bladder pain syndrome is lacking and is in the formative stages. The Workshop on Hunner lesion versus non‐Hunner lesion at the 2018 International Consultation on Interstitial Cystitis Japan discussed prevalence, performance and outcome of endoscopy, the role of histopathology, and markers. Methods A panel of experts reviewed the literature regarding Hunner lesion vs. non‐Hunner lesion interstitial cystitis/bladder pain syndrome. Results The prevalence of Hunner lesion has been reported to be 5–57%. Older age and smaller anatomic bladder capacity were associated with Hunner lesions. Cystoscopy using local anesthesia is not adequate in diagnosing interstitial cystitis but is needed to rule out confusable diseases. Cystoscopy with hydrodistention and redistention of the bladder is considered standard. A Hunner lesion is visualized as a quite typical inflammatory reaction: a reddened mucosal area with small vessels radiating towards a central scar, splitting at distension, usually associated with a waterfall bleeding pattern. Biopsies from the inflamed area show inflammatory infiltrates, granulation tissue, detrusor mastocytosis, and fibrin deposits. Ablation of Hunner lesions includes transurethral resection of lesions, fulguration, laser ablation, and cortical steroid injections. Mast cell density is a somewhat controversial matter, described differently in different studies: marked increase in Hunner lesion vs. non‐Hunner lesion in the majority of studies, no difference in a few. Nitric oxide appears to be a definitive marker in distinguishing Hunner lesion vs. non‐Hunner lesion disease. Macrophage migration inhibitory factor is elevated in Hunner lesion patients. Increased level of urinary proinflammatory genes expression has also been found in Hunner lesion subjects. Conclusions Hunner lesion patients are clinically and pathologically distinct from non‐Hunner lesion bladder pain syndrome patients.

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Comparison of deep phenotyping features of UCPPS with and without Hunner lesion: A MAPP‐II Research Network Study

Lai

Newcomb

Harte

et al. 2021

Neurourology and Urodynamics

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Objective: To use the phenotyping data from the MAPP-II Symptom Patterns Study (SPS) to compare the systemic features between urologic chronic pelvic pain syndrome (UCPPS) with Hunner lesion (HL) versus those without HL. Methods: We performed chart review on 385 women and 193 men with UCPPS who enrolled in the MAPP-II SPS. 223 had cystoscopy and documentation of HL status. Among them, 12.5% had HL and 87.5% did not. Results: UCPPS participants with HL were older, had increased nocturia, higher Interstitial Cystitis Symptom and Problem Indexes, and were more likely to report "painful urgency" compared with those without HL. On the other hand, UCPPS without HL reported more intense nonurologic pain, greater distribution of pain outside the pelvis, greater numbers of comorbid chronic overlapping pain conditions, higher fibromyalgia-like symptoms, and greater pain centralization, and were more likely to have migraine headache than those with HL. UCPPS without HL also had higher anxiety, perceived stress, and pain catastrophizing than those with HL. There were no differences in sex distribution, UCPPS symptom duration, intensity of urologic pain, distribution of genital pain, pelvic floor tenderness on pelvic examination, quality of life, depression, pain characteristics (nociceptive pain vs. neuropathic pain), mechanical hypersensitivity in the suprapubic area during quantitative sensory testing, and 3-year longitudinal pain outcome and urinary outcome between the two groups. Conclusions: UCPPS with HL displayed more bladder-centric symptom profiles, while UCPPS without HL displayed symptoms suggesting a more Abbreviations: COPC, chronic overlapping pain condition(s); HL, Hunner lesion; MAPP, multidisciplinary approach to the study of chronic pelvic pain; QST, quantitative sensory testing; SPS, symptom pattern study; UCPPS, urologic chronic pelvic pain syndrome.

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Elevated Urine Levels of Macrophage Migration Inhibitory Factor in Inflammatory Bladder Conditions: A Potential Biomarker for a Subgroup of Interstitial Cystitis/Bladder Pain Syndrome Patients

Cited by 28 publications

References 29 publications

Protease activated‐receptor 4 activation as a model of persistent bladder pain: Essential role of macrophage migration inhibitory factor and high mobility group box 1

Protease activated‐receptor 4 activation as a model of persistent bladder pain: Essential role of macrophage migration inhibitory factor and high mobility group box 1

Hunner lesion versus non‐Hunner lesion interstitial cystitis/bladder pain syndrome

Comparison of deep phenotyping features of UCPPS with and without Hunner lesion: A MAPP‐II Research Network Study

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