title: Establishment of a Novel Autoimmune Experimental Model of Bladder Pain Syndrome/Interstitial Cystitis in C57BL/6 Mice.
abstract: The aim of this study is to identify whether vaccinating twice with bladder homogenate can establish a new model of experimental autoimmune cystitis (EAC) in C57BL/6 strain mice. C57BL/6 mice were vaccinated with bladder homogenate in complete Freund's adjuvant (CFA) and boost immunized with bladder homogenate in incomplete Freund's adjuvant (IFA) after 2 weeks were used as the EAC model. Mice immunized with phosphate-buffered saline (PBS) in CFA or IFA were used as the control. Micturition habits and suprapubic-pelvic pain threshold were measured 4 weeks after primary immunization. Bladder to body weight ratios and expression of inflammatory cytokines and neurokinin 1 receptor (NK1R) were then examined. Histologic and immunohistochemical examination of the bladder was carried out, and IL-1β, IFN-γ, and TNF-α production by the kidneys, liver, and lungs was also tested. Double-immunized mice were extensively sensitive to pressure applied on the pelvic area (P < 0.001). Compared to single-immunized mice or controls, double-immunized mice showed more micturition frequency, lower urine output per micturition, higher bladder to body weight ratio, and significant elevation in the expression of inflammatory cytokines, including IL-1β, IL-4, IL-6, IL-10, IFN-γ, and TNF-α (all P < 0.05). NK1R gene expression was significantly increased in double-immunized mice compared to the other three groups (P < 0.001). A nonspecific immune response occurred in the liver but was much weaker than bladder inflammation. Our dual immunization EAC model in C57BL/6 mice can effectively mimic the symptoms and pathophysiologic characteristics of BPS/IC and thus can be widely used to investigate the pathogenesis and therapeutic strategies of BPS/IC.
authors.affiliation: Department of Urology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Er Road, Shanghai, 200025, China.
authors.forename: Xing-Wei
authors.initials: XW
authors.lastname: Jin
authors.affiliation: Department of Urology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Er Road, Shanghai, 200025, China.
authors.forename: Bo-Ke
authors.initials: BK
authors.lastname: Liu
authors.affiliation: Department of Urology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Er Road, Shanghai, 200025, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
authors.forename: Zhong-Hua
authors.initials: ZH
authors.lastname: Zhao
authors.affiliation: Department of Urology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Er Road, Shanghai, 200025, China. shaoyuan15@hotmail.com.|Department of Urology, Ruijin Hospital North, Shanghai Jiao Tong University School of Medicine, Shanghai, China. shaoyuan15@hotmail.com.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Shao
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases; D018856:Cystitis, Interstitial / Q000473:pathology*; D016207:Cytokines / Q000032:analysis; D004195:Disease Models, Animal; D007114:Immunization / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size / Q000276:immunology; D010146:Pain / Q000209:etiology*; D001743:Urinary Bladder / Q000473:pathology*; D014554:Urination
chemical_list: D016207:Cytokines
keywords: C57BL/6; autoimmune cystitis model; bladder pain syndrome; interstitial cystitis