Serum sphingosine-1-phosphate levels in bladder pain syndrome/interstitial cystitis patients: could it help in diagnosis?

  • Tariq AsiEmail author
  • Ahmet Asci
  • Mesut Altan
  • Ahmet Gudeloglu
  • Ali Ergen
Original Article



To find if there is any potential benefit of serum Sphingosine-1-Phosphate (S1P) level in the diagnosis of Bladder Pain Syndrome/Interstitial Cystitis (BPS/IC).

Methods and materials

Patients newly or previously diagnosed with BPS/IC between September 2017 and December 2018 were included. Healthy individuals who volunteered to enter the study were included as control group. The measurements of serum S1P in both groups were compared. Multiple regression analysis was conducted to find out the significant factors affecting S1P results.


A total of 47 BPS/IC patients and 47 healthy controls were included. BPS/IC patients were older than controls (48.5 ± 12.4 vs 38.9 ± 8.1 years, p < 0.001). The female-to-male ratio was 46/1 for patient group and 29/18 for controls. 68.1% (32/47) of BPS/IC patients had previous treatments. 55.3%(26/47) of patient group had accompanying medical or psychiatric disease.

The mean serum S1P level was notably elevated in BPS/IC group (median 213.6, mean ± SD 258.9 ± 167.2 vs median 125.4, mean ± SD 142.9 ± 54.8; p < 0.001). Using ROC curve analysis, a value of 165 was a good cutoff point between patient and control groups (AUC = 0.761, p < 0.001). On multiple regression analysis, being BPS/IC patient was the only significant predictor of a serum S1P level above the cutoff point documented on ROC analysis (OR 5.9; 95% CI 1.8–19.9; p = 0.004).


Sphingosine-1-phosphate (S1P) pathway seems to have a potential role in the pathogenesis of BPS/IC. High serum S1P level might support the diagnosis of BPS/IC.


Bladder pain syndrome interstitial cystitis serum sphingosine-1-phosphate diagnosis 


Authors’ contribution

TA, MA, AG, AE: Protocol/Project development. AA, TA, MA: Data collection or management. TA, AE: Data analysis. AA, TA: Manuscript writing/editing.


This research has been funded by Hacettepe University- Coordination of Scientific Research Projects.

Compliance with ethical standards

Conflict of ınterest

The authors declare that they have no conflict of interest.

Human and animal rights statements

This article does not contain any studies with human participants or animals performed by any ofthe authors.


  1. 1.
    Homma Y, Ueda T, Tomoe H et al (2016) Clinical guidelines for interstitial cystitis and hypersensitive bladder updated in 2015. 23:542–549Google Scholar
  2. 2.
    Suskind AM, Berry SH, Ewing BA et al (2013) The prevalence and overlap of interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome in men: results of the RAND Interstitial Cystitis Epidemiology male study. J Urol 189:141–145CrossRefGoogle Scholar
  3. 3.
    Berry SH, Elliott MN, Suttorp M et al (2011) Prevalence of symptoms of bladder pain syndrome/interstitial cystitis among adult females in the United States. J Urol 186:540–544CrossRefGoogle Scholar
  4. 4.
    Nickel JC (2004) Interstitial cystitis: a chronic pelvic pain syndrome. Med Clin N Am 88(467–481):xiiGoogle Scholar
  5. 5.
    Sant G (1997) Interstitial cystitis. Curr Opin Obstet Gynecol 9:332–336CrossRefGoogle Scholar
  6. 6.
    Payne CK, Joyce GF, Wise M et al (2007) Interstitial cystitis and painful bladder syndrome. J Urol 177:2042–2049CrossRefGoogle Scholar
  7. 7.
    Michael YL, Kawachi I, Stampfer MJ et al (2000) Quality of life among women with interstitial cystitis. J Urol 164:423–427CrossRefGoogle Scholar
  8. 8.
    Held PJ, Hanno PM, Wein AJ et al (1990) Epidemiology of Interstitial Cystitis: 2. In: Hanno PM, Staskin DR, Krane RJ, et al. (eds) Interstitial Cystitis. Springer, London, London, pp 29–48CrossRefGoogle Scholar
  9. 9.
    Grover S, Srivastava A, Lee R et al (2011) Role of inflammation in bladder function and interstitial cystitis. Therap Adv Urol 3:19–33CrossRefGoogle Scholar
  10. 10.
    Proia RL, Hla T (2015) Emerging biology of sphingosine-1-phosphate: its role in pathogenesis and therapy. J Clin Investig 125:1379–1387CrossRefGoogle Scholar
  11. 11.
    Clemens JQ, Meenan RT, Rosetti MC et al (2005) Prevalence and incidence of interstitial cystitis in a managed care population. J Urol 173:98–102 (discussion 102) CrossRefGoogle Scholar
  12. 12.
    Warren JW, Diggs C, Brown V et al (2006) Dysuria at onset of interstitial cystitis/painful bladder syndrome in women. Urology 68:477–481CrossRefGoogle Scholar
  13. 13.
    Porru D, Politano R, Gerardini M et al (2004) Different clinical presentation of interstitial cystitis syndrome. Int Urogynecol J Pelvic Floor Dysfunct 15:198–202CrossRefGoogle Scholar
  14. 14.
    Silk MR (1970) Bladder antibodies in interstitial cystitis. J Urol 103:307–309CrossRefGoogle Scholar
  15. 15.
    Birder LA (2019) Pathophysiology of interstitial cystitis. Int J Urol 26(Suppl 1):12–15CrossRefGoogle Scholar
  16. 16.
    Chung SD, Liu HT, Lin H et al (2011) Elevation of serum c-reactive protein in patients with OAB and IC/BPS implies chronic inflammation in the urinary bladder. Neurourol Urodyn 30:417–420CrossRefGoogle Scholar
  17. 17.
    Jiang YH, Peng CH, Liu HT et al (2013) Increased pro-inflammatory cytokines, C-reactive protein and nerve growth factor expressions in serum of patients with interstitial cystitis/bladder pain syndrome. PLoS ONE 8:e76779CrossRefGoogle Scholar
  18. 18.
    Liu HT, Kuo HC (2012) Increased urine and serum nerve growth factor levels in interstitial cystitis suggest chronic inflammation is involved in the pathogenesis of disease. PLoS ONE 7:e44687CrossRefGoogle Scholar
  19. 19.
    Lotz M, Villiger P, Hugli T et al (1994) Interleukin-6 and interstitial cystitis. J Urol 152:869–873CrossRefGoogle Scholar
  20. 20.
    Erickson DR, Tomaszewski JE, Kunselman AR et al (2005) Do the National Institute of Diabetes and Digestive and Kidney Diseases cystoscopic criteria associate with other clinical and objective features of interstitial cystitis? J Urol 173:93–97CrossRefGoogle Scholar
  21. 21.
    Kuo HC, Liu HT, Tyagi P et al (2010) Urinary Nerve Growth Factor Levels in Urinary Tract Diseases With or Without Frequency Urgency Symptoms. Lower Urinary Tract Sympt 2:88–94CrossRefGoogle Scholar
  22. 22.
    Blaho VA, Hla T (2014) An update on the biology of sphingosine 1-phosphate receptors. J Lipid Res 55:1596–1608CrossRefGoogle Scholar
  23. 23.
    Chalfant CE, Spiegel S (2005) Sphingosine 1-phosphate and ceramide 1-phosphate: expanding roles in cell signaling. J Cell Sci 118:4605–4612CrossRefGoogle Scholar
  24. 24.
    Oskeritzian CA, Alvarez SE, Hait NC et al (2008) Distinct roles of sphingosine kinases 1 and 2 in human mast-cell functions. Blood 111:4193–4200CrossRefGoogle Scholar
  25. 25.
    LaMontagne K, Littlewood-Evans A, Schnell C et al (2006) Antagonism of sphingosine-1-phosphate receptors by FTY720 inhibits angiogenesis and tumor vascularization. Can Res 66:221–231CrossRefGoogle Scholar
  26. 26.
    Gon Y, Wood MR, Kiosses WB et al (2005) S1P3 receptor-induced reorganization of epithelial tight junctions compromises lung barrier integrity and is potentiated by TNF. Proc Natl Acad Sci USA 102:9270–9275CrossRefGoogle Scholar
  27. 27.
    Ochodnicky P, Humphreys S, Eccles R et al (2012) Expression profiling of G-protein-coupled receptors in human urothelium and related cell lines. BJU Int 110:E293–300CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of UrologyHacettepe University HospitalsAnkaraTurkey

Personalised recommendations