Mast cells mediate the severity of experimental cystitis in mice

Purpose: We hypothesized that experimental cystitis induced by substance P (SP) or E. coli lipopolysaccharide (LPS) would be less severe in mice rende red mast cell deficient by genetic manipulation. Materials and Methods: Two strains of mast-cell deficient mice (WBB6F1- kit (W)/kit(W-v) or kit(W)/kit(W-v) and WC6GF1-Sl/Sld or Sl/Sld) and their cong enic, normal (+/+) counterparts were used. Cystitis was induced in female m ice by intravenous injection of SP (0.1 ml.; 10(-6) M) or E. coli LPS (0.1 ml.; 2 mg./ml.), and inflammation was assessed by Evans blue dye extravasat ion. In a separate group of kit(W)/kit(W-v) and congenic normal mice, cysti tis was induced by intravesical infusion of SP (0.05 ml.; 10(-5) M) or E. c oli LPS (0.05 ml.; 100 mu g./ml.) and compared with intravesical pyrogen-fr ee saline (0.05 ml.; 0.9%). Severity of cystitis was determined by histolog ical evaluation of the bladder wall 24 hours after intravesical infusions. Results: Intravenous SP or LPS stimulated increased plasma extravasation in congenic normal mice but not in mast cell-deficient mice. Intravesical SP or LPS resulted in increased edema, leukocytic infiltration, and hemorrhage within the bladder wall in congenic normal mice, but the only histological evidence of inflammation in the bladders of kit(W)/kit(W-v) mice was incre ased hemorrhage in response to LPS. Conclusions: This study indicates that mast cells modulate the inflammatory response of the bladder to SP and LPS in mice. Although clinical trials of the use of antihistamines to treat or prevent cystitis have not been succe ssful, these results suggest that therapies directed toward preventing mast cell activation may yet prove effective in treating cystitis.