Cytokines in Bladder Pain Syndrome: A Review of the Literature

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This literature review identified 36 significantly elevated cytokines in the serum, urine, or bladder tissue of bladder pain syndrome patients, suggesting panels of inflammatory mediators may be needed for diagnosis.

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This paper is a literature review examining elevated cytokines associated with bladder pain syndrome (also called painful bladder syndrome or interstitial cystitis), focusing on urinary, serum, and bladder tissue measurements across 22 included studies. Using PubMed search terms for bladder pain syndrome and cytokines/inflammation, it reports that 36 cytokines are statistically significantly elevated, spanning interleukins (14), CXC chemokines (5), and C–C chemokines (7). The review highlights specific CXC and C–C mediators (e.g., CXCL-1, CXCL-8, CXCL-9, CXCL-10, CXCL-11 and CCL2, CCL4, CCL5, CCL7, CCL11) and notes the limitation that no single cytokine is likely to serve as an adequate biomarker, implying biomarker panels may better capture heterogeneous inflammatory pathways. This paper is centrally about endometriosis — it does not focus on endometriosis, but discusses symptom overlap between bladder pain syndrome and chronic pelvic pain disorders including endometriosis as a rationale for the diagnostic challenges it addresses.

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Abstract

INTRODUCTION AND HYPOTHESIS: Bladder pain syndrome (BPS) is poorly understood with both the aetiology and pathophysiology being unknown. Symptoms overlap with other disorders, such as overactive bladder (OAB) and chronic pelvic pain disorders such as endometriosis, making a consensus on how to diagnosis and manage patients challenging. The development of biomarkers for BPS may be the key to understanding more about its pathophysiology, as well as aiding diagnosis, subclassification, and discovering new drug targets for its management. As inflammation is widely understood to hold a central role in BPS, the evaluation of cytokines has gained interest. This article summarises the current literature and understanding of urinary, serum, and bladder tissue cytokines found elevated in patients with bladder pain syndrome. METHODS: literature search using Pub Med with the keywords "bladder pain syndrome", "painful bladder syndrome", "bladder pain", "Interstitial cystitis" AND "cytokines" or "inflammation". This study was except from institutional approval. RESULTS: Thirty-six cytokines have been identified as being statistically significantly elevated in either the serum, urine, or bladder tissue of patients with bladder pain syndrome in the 22 studies identified in this review of the literature. These cytokines include those from the interleukin group (n = 14), the CXC chemokine group (n = 5), and the C-C chemokine group (n = 7). CONCLUSIONS: CXCL-1, CXCL-8, CXCL-9, CXCL-10, CXCL-11 from the CXC chemokine group, and CCL2, CCL4, CCL5, CCL7, and CCL11 from the C-C chemokine group have been found to be significantly elevated in patients with bladder pain in the literature. Many of these analytes also have supporting evidence for their roles in bladder pain from animal models and studies in other chronic inflammatory conditions. It is likely that a single cytokine will not serve as an adequate biomarker of disease in bladder pain syndrome for either diagnosis or disease severity. Instead, panels of inflammatory mediators may reveal more about the different pathways of inflammation leading to similar presentations of bladder pain in patients.
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Abstract

Introduction and hypothesis Bladder pain syndrome (BPS) is poorly understood with both the aetiology and pathophysiology being unknown. Symptoms overlap with other disorders, such as overactive bladder (OAB) and chronic pelvic pain disorders such as endometriosis, making a consensus on how to diagnosis and manage patients challenging. The development of biomarkers for BPS may be the key to understanding more about its pathophysiology, as well as aiding diagnosis, subclassification, and discovering new drug targets for its management. As inflammation is widely understood to hold a central role in BPS, the evaluation of cytokines has gained interest. This article summarises the current literature and understanding of urinary, serum, and bladder tissue cytokines found elevated in patients with bladder pain syndrome.

Methods

literature search using Pub Med with the keywords “bladder pain syndrome”, “painful bladder syndrome”, “bladder pain”, “Interstitial cystitis” AND “cytokines” or “inflammation”. This study was except from institutional approval.

Results

Thirty-six cytokines have been identified as being statistically significantly elevated in either the serum, urine, or bladder tissue of patients with bladder pain syndrome in the 22 studies identified in this review of the literature. These cytokines include those from the interleukin group (n = 14), the CXC chemokine group (n = 5), and the C–C chemokine group (n = 7).

Conclusions

CXCL-1, CXCL-8, CXCL-9, CXCL-10, CXCL-11 from the CXC chemokine group, and CCL2, CCL4, CCL5, CCL7, and CCL11 from the C–C chemokine group have been found to be significantly elevated in patients with bladder pain in the literature. Many of these analytes also have supporting evidence for their roles in bladder pain from animal models and studies in other chronic inflammatory conditions. It is likely that a single cytokine will not serve as an adequate biomarker of disease in bladder pain syndrome for either diagnosis or disease severity. Instead, panels of inflammatory mediators may reveal more about the different pathways of inflammation leading to similar presentations of bladder pain in patients. Similar content being viewed by others

References

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Brief Summary Literature review of cytokines in the urine, serum, and bladder tissue of those with bladder pain syndrome. Rights and permissions About this article Cite this article Lemmon, B., Kyrgiou, M., Mullins, E. et al. Cytokines in Bladder Pain Syndrome: A Review of the Literature. Int Urogynecol J 35, 1119–1129 (2024). https://doi.org/10.1007/s00192-024-05778-4 Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s00192-024-05778-4

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chronic_pelvic_painendometriosisinterstitial_cystitis

MeSH descriptors

Cystitis, Interstitial Cystitis, Interstitial Cystitis, Interstitial Cystitis, Interstitial Cystitis, Interstitial Cystitis, Interstitial Cystitis, Interstitial Cystitis, Interstitial Cystitis, Interstitial Cystitis, Interstitial Cystitis, Interstitial Cystitis, Interstitial Cystitis, Interstitial Cystitis, Interstitial Cystitis, Interstitial Cystitis, Interstitial Cystitis, Interstitial Cystitis, Interstitial Cystitis, Interstitial Cytokines

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