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Effect of Intravesical Administration of Steroid Enemas on an Experimental Autoimmune Interstitial Cystitis-Like
Kimio Sugaya1, Saori Nishijima1, Katsumi Kadekawa1
1Southern Knights' Laboratory, Okinawa, Japan.
Aim:
Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic, non-bacterial cystitis presenting with bladder pain, frequent urination, and Hunner's lesions. Current therapies, including dimethyl sulfoxide (DMSO) instillation, provide temporary relief but often cause procedural pain. Steroid enemas, used for ulcerative colitis and suitable for self-administration, may offer a novel intravesical treatment option.
Methods:
An experimental autoimmune interstitial cystitis (EAIC) mouse model was induced by immunization with bladder homogenate. Four weeks later, EAIC mice received intravesical phosphate-buffered saline (PBS), 50% DMSO, or a steroid enema formulation containing prednisolone phosphate (Predonema®). Controls received PBS. Outcomes included locomotor activity, cystometry, histopathology, and bladder gene expression by RT-qPCR.
Results:
EAIC mice showed increased locomotor activity, shortened bladder contraction intervals, urothelial irregularity, and upregulated inflammatory cytokines (IL-1β, IL-6), chemokines (CCL2, CXCL1, CXCL10), COX-2, NGF, VEGF-A, vimentin, and uroplakin-2. DMSO transiently reduced locomotor activity, worsened epithelial thickening, cellular infiltration, and decreased body weight. In contrast, steroid enema instillation preserved urothelial architecture, reduced inflammation, suppressed gene upregulation, normalized bladder function, and alleviated hyperactivity without adverse effects.
Conclusions:
EAIC mice reproduce pathological and functional features of IC/BPS. Intravesical steroid enema administration showed superior anti-inflammatory and functional benefits compared with DMSO, without apparent tissue damage or disease-associated hyperactivity. Although the effectiveness of steroid enemas might be partially influenced by the effect of thickening agents used as enema additives, this approach could represent a practical, patient-friendly therapy for IC/BPS, supporting further preclinical and clinical evaluation.
