Skip to main content

Advertisement

SpringerLink
Log in

Mapping the cytokine profile of painful bladder syndrome/interstitial cystitis in human bladder and urine specimens

  • Original Article
  • Published:
World Journal of Urology Aims and scope Submit manuscript

Abstract

Purpose

This study investigated the cytokine profile in bladder tissue and urine of painful bladder syndrome/interstitial cystitis (PBS/IC) patients.

Methods

Multiplex analysis of 23 cytokines was performed with a multiple antigen bead assay (Luminex 100 IS) on cold cup bladder biopsy and urine specimens collected during cystoscopy with hydrodistention (HD) under general anesthesia from 10 PBS/IC patients (ICS definition). Collected tissue specimens and urine from pre-HD and post-HD (mean 27 days) were compared to banked urine and tissue specimens (n = 10) collected from control subjects without PBS/IC symptoms.

Results

Univariate comparison of bladder tissue levels found significant elevation of IL-16, IL-18, CTACK, ICAM-1, MCP-3, SCGFβ, TRAIL, and VCAM-1 in PBS/IC relative to controls. Multivariate analysis revealed VCAM-1 and ICAM-1 were responsible for the discrimination of both tissue and urine of PBS/IC from controls. Urine levels of MCP-3 and TRAIL were significantly reduced a month after HD in concert with improvement in standardized measures of clinical symptoms (pain, urgency, and frequency (PUF) overall score [mean 25.8 ± 5.5 vs. 20.3 ± 7, p = 0.04] and symptom score [mean 18.2 ± 3.2 vs. 12.2 ± 5.9; p = 0.009]). Post-HD urine levels of MCSF(r = 0.88; p = 0.003), MCP-3 (r = 0.81; p = 0.01), SDF1α (r = 0.82; p = 0.01), and IL-18 (r = 0.64; p = 0.08) positively correlated with improved symptom scores.

Conclusions

These results indicate significant elevation of cytokines in PBS/IC bladder tissue relative to controls. Significant reduction in post-HD urine levels of MCP-3 and TRAIL relative to pre-HD in PBS/IC was associated with clinical improvement (as measured by PBS/IC symptom scores) to qualify them as biomarker candidates.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Erickson DR, Xie SX, Bhavanandan VP, Wheeler MA, Hurst RE, Demers LM et al (2002) A comparison of multiple urine markers for interstitial cystitis. J Urol 167:2461–2469

    Article  PubMed  CAS  Google Scholar 

  2. Ogawa T, Homma T, Igawa Y, Seki S, Ishizuka O, Imamura T et al (2010) CXCR3 binding chemokine and TNFSF14 over expression in bladder urothelium of patients with ulcerative interstitial cystitis. J Urol 183:1206–1212

    Article  PubMed  CAS  Google Scholar 

  3. Brewer ME, White WM, Klein FA, Klein LM, Waters WB (2007) Validity of pelvic pain, urgency, and frequency questionnaire in patients with interstitial cystitis/painful bladder syndrome. Urology 70:646–649

    Article  PubMed  Google Scholar 

  4. Tyagi P, Barclay D, Zamora R, Yoshimura N, Peters K, Vodovotz Y et al (2010) Urine cytokines suggest an inflammatory response in the overactive bladder: a pilot study. Int Urol Nephrol 42:629–635

    Article  PubMed  Google Scholar 

  5. George SK, Dipu MT, Mehra UR, Singh P, Verma AK, Ramgaokar JS (2006) Improved HPLC method for the simultaneous determination of allantoin, uric acid and creatinine in cattle urine. J Chromatogr, B: Anal Technol Biomed Life Sci 832:134–137

    Article  CAS  Google Scholar 

  6. Smaldone MC, Vodovotz Y, Tyagi V, Barclay D, Philips BJ, Yoshimura N et al (2009) Multiplex analysis of urinary cytokine levels in rat model of cyclophosphamide-induced cystitis. Urology 73:421–426

    Article  PubMed  Google Scholar 

  7. Zhang Z, Cherryholmes G, Mao A, Marek C, Longmate J, Kalos M et al (2008) High plasma levels of MCP-1 and eotaxin provide evidence for an immunological basis of fibromyalgia. Exp Biol Med (Maywood) 233:1171–1180

    Article  CAS  Google Scholar 

  8. Bouchelouche K, Alvarez S, Andersen L, Nordling J, Horn T, Bouchelouche P (2004) Monocyte chemoattractant protein-1 production by human detrusor smooth muscle cells. J Urol 171:462–466

    Article  PubMed  CAS  Google Scholar 

  9. Tyagi P, Killinger K, Tyagi V, Nirmal J, Peters K (2012) Urinary chemokines as Non-Invasive predictors of Ulcerative interstitial cystitis. J Urol 187:1275–1279

    Article  Google Scholar 

  10. Malaviya R, Ikeda T, Ross E, Abraham SN (1996) Mast cell modulation of neutrophil influx and bacterial clearance at sites of infection through TNF-alpha. Nature 381:77–80

    Article  PubMed  CAS  Google Scholar 

  11. Dodd LG, Tello J (1998) Cytologic examination of urine from patients with interstitial cystitis. Acta Cytol 42:923–927

    Article  PubMed  CAS  Google Scholar 

  12. Kutlu O, Akkaya E, Koksal IT, Bassorgun IC, Ciftcioglu MA, Sanlioglu S et al (2010) Importance of TNF-related apoptosis-inducing ligand in pathogenesis of interstitial cystitis. Int Urol Nephrol 42:393–399

    Article  PubMed  CAS  Google Scholar 

  13. Wei W, Wang D, Shi J, Xiang Y, Zhang Y, Liu S et al (2010) Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) induces chemotactic migration of monocytes via a death receptor 4-mediated RhoGTPase pathway. Mol Immunol 47:2475–2484

    Article  PubMed  CAS  Google Scholar 

  14. McGrath EE, Marriott HM, Lawrie A, Francis SE, Sabroe I, Renshaw SA et al (2011) TNF-related apoptosis-inducing ligand (TRAIL) regulates inflammatory neutrophil apoptosis and enhances resolution of inflammation. J Leukoc Biol 90:855–865

    Article  PubMed  CAS  Google Scholar 

  15. Rosevear HM, Lightfoot AJ, O’Donnell MA, Griffith TS (2009) The role of neutrophils and TNF-related apoptosis-inducing ligand (TRAIL) in bacillus Calmette-Guerin (BCG) immunotherapy for urothelial carcinoma of the bladder. Cancer Metastasis Rev 28:345–353

    Article  PubMed  Google Scholar 

  16. Ottem DP, Teichman JM (2005) What is the value of cystoscopy with hydrodistension for interstitial cystitis? Urology 66:494–499

    Article  PubMed  Google Scholar 

  17. Chai TC, Zhang CO, Shoenfelt JL, Johnson HW Jr, Warren JW, Keay S (2000) Bladder stretch alters urinary heparin-binding epidermal growth factor and antiproliferative factor in patients with interstitial cystitis. J Urol 163:1440–1444

    Article  PubMed  CAS  Google Scholar 

  18. Liu HT, Tyagi P, Chancellor MB, Kuo HC (2009) Urinary nerve growth factor level is increased in patients with interstitial cystitis/bladder pain syndrome and decreased in responders to treatment. BJU Int 104:1476–1481

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by the Samuel Wilan Research Fund for Interstitial Cystitis, NIH grants (DK57267 and DK88836) and Department of Defense grant PR110326.

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Department of Urology, University of Pittsburgh School of Medicine, Suite 700 Kaufmann Medical Building, 3471 Fifth Avenue, Pittsburgh, PA, 15213, USA

    Anthony T. Corcoran, Naoki Yoshimura, Vikas Tyagi, Bruce Jacobs, Wendy Leng & Pradeep Tyagi

Authors
  1. Anthony T. Corcoran
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Naoki Yoshimura
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Vikas Tyagi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Bruce Jacobs
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Wendy Leng
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Pradeep Tyagi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Naoki Yoshimura.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Corcoran, A.T., Yoshimura, N., Tyagi, V. et al. Mapping the cytokine profile of painful bladder syndrome/interstitial cystitis in human bladder and urine specimens. World J Urol 31, 241–246 (2013). https://doi.org/10.1007/s00345-012-0852-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00345-012-0852-y

Keywords

Search

Navigation