Immunomodulation-A Molecular Solution to Treating Patients with Severe Bladder Pain Syndrome?
Bladder pain syndrome
Immunotherapy
Interleukin-1 receptor antagonist
Interstitial cystitis
Journal
European urology open science
ISSN: 2666-1683
Titre abrégé: Eur Urol Open Sci
Pays: Netherlands
ID NLM: 101771568
Informations de publication
Date de publication:
Sep 2021
Sep 2021
Historique:
accepted:
07
07
2021
entrez:
1
9
2021
pubmed:
2
9
2021
medline:
2
9
2021
Statut:
epublish
Résumé
Patients with bladder pain syndrome experience debilitating pain and extreme frequency of urination. Numerous therapeutic approaches have been tested, but as the molecular basis of disease has remained unclear, specific therapies are not available. Recently, a systematic gene deletion strategy identified interleukin-1 (IL-1) hyperactivation as a cause of severe cystitis in a murine model. Treatment with an IL-1 receptor antagonist (IL-1RA) restored health in genetically susceptible mice, linking IL-1-dependent inflammation to pain and pathology in the bladder mucosa. The study objective was to investigate whether IL-1RA treatment might be beneficial in patients with bladder pain syndrome. Patients diagnosed with bladder pain syndrome were invited to participate and subjected to daily IL-1RA injections for 1 wk, followed by a treatment break. Patients with other urological disorders accompanied by pain were included as controls. When symptoms returned, treatment was resumed and responding patients were maintained on treatment long term, with individualized dosing regimens. Symptom scores were recorded and molecular effects were quantified by neuropeptide and gene expression analysis. DNA samples were subjected to exome genotyping. IL-1RA treatment reduced bladder pain and the frequency of urination in 13/17 patients ( In this clinical study, IL-1RA treatment is proposed to reduce chronic bladder pain, immediately and in the long term. Despite the limited number of study patients, the potent acute effect and lasting symptom relief indicate that this therapeutic approach may be worth exploring in controlled clinical trials. Treatment with an interleukin-1 (IL-1) receptor antagonist is proposed for treating bladder pain syndrome, as it can result in symptom relief and increase quality of life. Reduced neuroinflammation and IL-1 signaling provided molecular evidence of the treatment effects.
Sections du résumé
BACKGROUND
BACKGROUND
Patients with bladder pain syndrome experience debilitating pain and extreme frequency of urination. Numerous therapeutic approaches have been tested, but as the molecular basis of disease has remained unclear, specific therapies are not available.
OBJECTIVE
OBJECTIVE
Recently, a systematic gene deletion strategy identified interleukin-1 (IL-1) hyperactivation as a cause of severe cystitis in a murine model. Treatment with an IL-1 receptor antagonist (IL-1RA) restored health in genetically susceptible mice, linking IL-1-dependent inflammation to pain and pathology in the bladder mucosa. The study objective was to investigate whether IL-1RA treatment might be beneficial in patients with bladder pain syndrome.
DESIGN SETTING AND PARTICIPANTS
METHODS
Patients diagnosed with bladder pain syndrome were invited to participate and subjected to daily IL-1RA injections for 1 wk, followed by a treatment break. Patients with other urological disorders accompanied by pain were included as controls.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS
METHODS
When symptoms returned, treatment was resumed and responding patients were maintained on treatment long term, with individualized dosing regimens. Symptom scores were recorded and molecular effects were quantified by neuropeptide and gene expression analysis. DNA samples were subjected to exome genotyping.
RESULTS AND LIMITATIONS
CONCLUSIONS
IL-1RA treatment reduced bladder pain and the frequency of urination in 13/17 patients (
CONCLUSIONS
CONCLUSIONS
In this clinical study, IL-1RA treatment is proposed to reduce chronic bladder pain, immediately and in the long term. Despite the limited number of study patients, the potent acute effect and lasting symptom relief indicate that this therapeutic approach may be worth exploring in controlled clinical trials.
PATIENT SUMMARY
RESULTS
Treatment with an interleukin-1 (IL-1) receptor antagonist is proposed for treating bladder pain syndrome, as it can result in symptom relief and increase quality of life. Reduced neuroinflammation and IL-1 signaling provided molecular evidence of the treatment effects.
Identifiants
pubmed: 34467240
doi: 10.1016/j.euros.2021.07.003
pii: S2666-1683(21)00134-8
pmc: PMC8385293
doi:
Types de publication
Journal Article
Langues
eng
Pagination
49-58Informations de copyright
© 2021 The Authors.
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