Hypothesis / aims of study
Interstitial cystitis/Bladder pain syndrome (IC/BPS) is a debilitating condition characterized by pain, pressure or discomfort perceived to be related to the urinary bladder. Despite its well-recognized impact on patients, society, and healthcare systems, effective treatments remain lacking for IC/BPS. Effective preclinical models are needed to study disease pathophysiology and support the development and testing of novel therapies. Lipopolysaccharide (LPS) and cyclophosphamide (CYP)–induced models, have most commonly been used to study disease mechanisms; however, their biological relevance to specific inflammatory and remodelling pathways remains unclear. In this study, we aimed to systematically characterize and compare the histopathological and immunohistochemical features of LPS and CYP rat models of IC/BPS.
Study design, materials and methods
Female rats were allocated to LPS (intravesical - IV), CYP (intraperitoneal - IP), and PBS control groups. IC/BPS was induced using established protocols, and bladder tissues were harvested on day 7. Histological evaluation was performed using hematoxylin–eosin staining. A semi-quantitative scoring system (0–3) was applied to assess inflammatory cell infiltration, tissue architecture disruption, and stromal/collagen disorganization. Immunohistochemical analyses were performed for integrin beta-1 (ITGB1), monocyte chemoattractant protein-1 (MCP-1), and chitinase-3-like protein 1 (CHI3L1). Marker expression was evaluated in the urothelium, lamina propria, and smooth muscle layers by blinded observers.
Results
Distinct histological and immunohistochemical patterns were observed in both groups. The LPS model demonstrated a severe inflammatory phenotype, characterized by widespread inflammatory cell infiltration, marked disruption of urothelial integrity, and pronounced stromal disorganization, resulting in maximum histological scores (3) across all evaluated domains. In contrast, the CYP model exhibited a moderate degree of injury (score 2), with partial preservation of tissue architecture, persistent stromal irregularity, and increased cellularity. Control groups showed intact urothelium, preserved stromal organization, and absence of inflammatory infiltration (score 0) (Figure 1).
Immunohistochemical analysis revealed increased expression of ITGB1, MCP-1, and CHI3L1 in both LPS and CYP groups compared to controls; however, their spatial distribution and intensity differed significantly (Figure 2). In the LPS model, staining was diffuse and strongly associated with areas of urothelial damage and dense inflammatory infiltrates, indicating robust immune activation and acute inflammatory response. MCP-1 and CHI3L1 expression were particularly prominent in regions rich in inflammatory cells, consistent with monocyte/macrophage recruitment.
In contrast, the CYP model demonstrated a more localized staining pattern, predominantly within the lamina propria and perivascular regions. ITGB1 expression was associated with fibroblasts, endothelial cells, and smooth muscle, suggesting activation of cell–extracellular matrix interactions. CHI3L1 expression in this group was more closely linked to stromal remodelling and early fibrotic processes rather than purely inflammatory activity.
Interpretation of results
Although both models reproduce features of bladder injury, they represent biologically distinct pathological processes. The LPS model predominantly reflects acute, inflammation-driven tissue damage, whereas the CYP model is characterized by urothelial toxicity accompanied by tissue remodelling and early fibrosis. Differential expression and localization of ITGB1, MCP-1, and CHI3L1 support divergence along the inflammation–repair–fibrosis axis.