Intravesical Nanocrystalline Silver Decreases Experimental Bladder Inflammation

Purpose: Interstitial cystitis is a sterile bladder inflammatory disease characterized by pelvic pain, urinary urgency and frequency. Nanocrystalline silver has anti-inflammatory properties, prompting us to investigate its effect in experimental bladder inflammation. Materials and Methods: Nanocrystalline silver (0.01%, 0.05%, 0.1%, 0.5% or 1%) or phosphate buffered saline (Invitrogen™) (0.5 ml) was introduced intravesically in Sprague-Dawley female rat (Charles River Laboratories, Wilmington, Massachusetts) bladders for 20 minutes, followed by vehicle or protamine sulfate (10 mg/ml for 30 minutes) and lipopolysaccharide (Sigma®) (2 mg/ml for 45 minutes). Urine was collected throughout for histamine assay. The catheter was removed, the rat was returned to its cage and 4 hours later it was sacrificed. The bladder was harvested, minced and cultured overnight. The medium was collected for tumor necrosis factor-α assay. Results: Mean ± SD total urine histamine increased from 270 ± 190 ng in 4 controls to 842 ± 239 ng after protamine sulfate/lipopolysaccharide and it decreased to 505 ± 187 ng in 6 animals after pretreatment with 1% nanocrystalline silver (p = 0.036). Tumor necrosis factor-α release in explant medium increased from 0.02 ± 0.03 pg/mg in 6 controls to 0.28 ± 0.15 pg/mg in 14 animals after treatment with protamine sulfate/lipopolysaccharide and it decreased to 0.12 ± 0.11 pg/mg in 10 animals pretreated with nanocrystalline silver (p = 0.009). Nanocrystalline silver was not effective at less than 1% and at 1% alone it released 0.05 ± 0.07 pg/mg tumor necrosis factor-α in 7 rats (vs phosphate buffered saline in 6, p = 0.387). Nanocrystalline silver (1%) significantly decreased bladder inflammation and mast cell activation. These effects were apparent even 4 days later. Conclusions: Intravesical administration of nanocrystalline silver (1%) decreased urine histamine, bladder tumor necrosis factor-α and mast cell activation without any toxic effect. This action may be useful for interstitial cystitis.