Local immune response in patients with classic and nonulcer type of interstitial cystitis/bladder pain syndrome

Cover Page

Cite item


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 (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, TNFα. Statistical processing of the results was carried out using the Statistica 6 software (StatSoft, USA). The Student’s t-test, Spearman’s correlation coefficient were calculated. In patients with Hunner's ulcer, 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), TNFα — 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 TNFα 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.

About the authors

R. F. Sholan

Republican Centre of Diagnosis and Treatment of the Health Ministry of Azerbaijan

Author for correspondence.
Email: ittihaf@yahoo.com
ORCID iD: 0000-0002-1047-167X

Rashad Farhad ogly Sholan - PhD (Medicine), Head of the Department of Kidney Diseases and Transplantology, Republican Centre of Diagnosis and Treatment of the Health Ministry of Azerbaijan.

AZ1122, Baku, Tbilisi pr., 147.

Phone: +994 50-212-53-57



  1. Зайцев А.В., Шаров М.Н., Ибрагимов Р.А., Нахрапов Д.И., Пушкарь Д.Ю. Синдром болезненного мочевого пузыря/интерстициальный цистит: современные подходы к диагностике и лечению // Врач скорой помощи. 2018. № 8. С. 16–26. doi: 10.21886/2308-6424-2018-6-3-26-35
  2. Кузьмин И.В., Игнашов Ю.А., Слесаревская М.Н., Аль-Шукри С.Х. Синдром болезненного мочевого пузыря у женщин: критерии эффективности и прогнозирование результатов лечения // Экспериментальная и клиническая урология. 2020. № 2. С. 142–148. doi: 10.29188/2222-8543-2020-12-2-142-148
  3. Лоран О.Б., Синякова Л.А., Митрохин А.А., Плесовский А.М., Штейнберг М.Л., Винарова Н.А. Современный взгляд на проблему интерстициального цистита // Медицинский совет. 2011. № 11–12. С. 15–19.
  4. Онопко В.Ф., Кириленко Е.А., Баранова Е.О., Голубева В.С. Интерстициальный цистит или синдром болезненного мочевого пузыря: современный взгляд на проблему // Acta Biomedica Scientifica. 2016. Т. 1, № 1. С. 65–69. doi: 10.12737/21489
  5. Akiyama Y., Morikawa T., Maeda D., Shintani Y., Niimi A., Nomiya A., Nakayama A., Igawa Y., Fukayama M., Homma Y. Increased CXCR3 expression of infiltrating plasma cells in Hunner type interstitial cystitis. Sci. Rep., 2016, vol. 6: 28652. doi: 10.1038/srep28652
  6. Argade S., Chermansky C., Tyagi P. Biomarkers for interstitial cystitis/painful bladder syndrome. Womens Health (Lond), 2016, vol. 12, no. 1, pp. 87–90. doi: 10.2217/whe.15.93
  7. Bayrak O., Seckiner I., Solakhan M., Karakok M., Erturhan S.M., Yagci F. Effects of intravesical dexpanthenol use on lipid peroxidation and bladder histology in a chemical cystitis animal model. Urology, 2012, vol. 79, pp. 1023–1026. doi: 10.1016/j.urology.2012.01.025
  8. Bjorling D.E., Jerde T.J., Zine M.J., Busser B.W., Saban M.R., Sabanet R. Mast cells mediate the severity of experimental cystitis in mice. J. Urology, 1999, vol. 162, no. 1, pp. 231–236. doi: 10.1097/00005392-199907000-00073
  9. Chung S.D., Liao C.H., Chen Y.C., Kuo H.C. Urgency severity scale could predict urodynamic detrusor overactivity in patients with overactive bladder syndrome. Neurourol. Urodyn., 2011, vol. 30, pp. 1300–1304. doi: 10.1002/nau.21057
  10. Fall M., Peeker R. Classic interstitial cystitis: unrelated to BPS. Curr. Bladder Dysfunct. Rep., 2015, vol. 10, pp. 95–102. doi: 10.1007/s11884-014-0273-4
  11. Furuta A., Suzuki Y., Egawa S., Yamamoto T., Yoshimura N. Pathophysiology of interstitial cystitis with or without Hunner lesion. Int. J. Urol., 2019, vol. 26, no. 1, pр. 77–78. doi: 10.1111/iju.13980
  12. Gamper M., Regauer S., Welter J., Eberhard J., Viereck V. Are mast cells still good biomarkers for bladder pain syndrome/interstitial cystitis? J. Urology, 2015, vol. 193, pp. 1994–2000. doi: 10.1016/j.juro.2015.01.036
  13. Gillenwater J.Y., Wein A.J. Summary of the National Institute of Arthritis, Diabetes and Kidney Diseases. Workshop on interstitial cystitis. National Institutes of Health, Bethesda, Maryland, August 28–29, 1987. J. Urology, 1988, vol. 140, pp. 203–206. doi: 10.1016/s0022-5347(17)41529-1
  14. Gonzalez E.J., Arms L., Vizzard M.A. The role(s) of cytokines/chemokines in urinary bladder inflammation and dysfunction. Biomed Res. Int., 2014, vol. 2014: 120525. doi: 10.1155/2014/120525
  15. Grover S., Srivastava A., Lee R., Tewari A.K. Role of inflammation in bladder function and interstitial cystitis. Ther. Adv. Urol., 2011, vol. 3, no. 1, рр. 19–33. doi: 10.1177/1756287211398255
  16. Homma Y., Ueda T., Tomoe H., Lin A.T., Kuo H.C., Lee M.H., Oh J.S., Kim J.C., Lee K.S. Clinical guidelines for interstitial cystitis and hypersensitive bladder updated in 2015. Int. J. Urology, 2016, vol. 23, pp. 542–549. doi: 10.1111/iju.13118
  17. Ke Q.-S., Kuo H.-C. Pathophysiology of interstitial cystitis/bladder pain syndrome. Tzu Chi Med. J., 2015, vol. 27, no. 4, pр. 139–144. doi: 10.1016/j.tcmj.2015.09.006
  18. Liu H.-T., Kuo H.-C. Biomarkers for patients with interstitial cystitis/bladder pain syndrome. Urol. Sci., 2015, vol. 26, no. 4, pp. 225–229. doi: 10.1016/j.urols.2015.02.002
  19. Logadottir Yr., Delbro D., Lindholm C., Fall M., Peeker R. Inflammation characteristics in bladder pain syndrome ESSIC type 3C/classic interstitial cystitis. Int. J. Urol., 2014, vol. 21, no. 1, рр. 75–78. doi: 10.1111/iju.12370
  20. Sant G.R., Kempuraj D., Marchand J.E., Theoharides T.C. The mast cell in interstitial cystitis: role in pathophysiology and pathogenesis. Urology, 2007, vol. 69, no. 4A, pp. 34–40. doi: 10.1016/j.urology.2006.08.1109
  21. Theoharides T.C., Alysandratos K.-D., Angelidou A., Delivanis D.-A., Sismanopoulos N., Zhang B., Asadi S., Vasiadi M., Weng Z., Minati A., Kalogeromitros D. Mast cells and inflammation. Biochim. Biophys. Acta, 2012, vol. 1822, no. 1, pp. 21–33. doi: 10.1016/j.bbadis.2010.12.014
  22. Vera P.L., Preston D.M., Moldwin R.M., Erickson D.R., Mowlazadeh B., Ma F., Kouzoukas D.E., Meyer-Siegler K.L., Fall M. 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. Urology, 2018, vol. 116, pp. 55–62. doi: 10.1016/j.urology.2018.02.039
  23. Wang X., Liu W., O’Donnell M., Lutgendorf S., Bradley C., Schrepf A., Liu L., Kreder K., Luo Y. Evidence for the role of mast cells in cystitis-associated lower urinary tract dysfunction: a multidisciplinary approach to the study of chronic pelvic pain research network animal model study. PLoS One, 2016, vol. 11, no. 12: e0168772. doi: 10.1371/journal.pone.0168772
  24. WMA. Declaration of Helsinki Ethical Principles for medical research involving human subjects. JAMA, 2013, vol. 310, no. 20, pp. 2191–2194. doi: 10.1001/jama.2013.281053

Supplementary files

There are no supplementary files to display.

Copyright (c) 2021 Sholan R.F.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77 - 64788 от 02.02.2016.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies