Intravesical nanocrystalline silver decreases experimental bladder inflammation.
OBJECTIVE
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.


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-alpha 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-alpha 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-alpha 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-alpha and mast cell activation without any toxic effect. This action may be useful for interstitial cystitis.
Boucher
W
W
Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine and Tufts-New England Medical Center, Boston, Massachusetts 02111, USA.
Stern
J M
JM
Kotsinyan
V
V
Kempuraj
D
D
Papaliodis
D
D
Cohen
M S
MS
Theoharides
T C
TC
D000283:Administration, Intravesical; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D018856:Cystitis, Interstitial / Q000188:drug therapy*; D004195:Disease Models, Animal; D005260:Female; D007249:Inflammation; D053768:Metal Nanoparticles / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012834:Silver / Q000008:administration & dosage*
D000893:Anti-Inflammatory Agents; D012834:Silver