Intravesical suplatast tosilate (IPD-1151T) inhibits experimental bladder inflammation.

Abstract

PURPOSE:

Interstitial cystitis is a painful bladder disease characterized by urgency, frequency and variable inflammation but there is no curative therapy. Suplatast tosilate (IPD-1151T) is an immunoregulatory compound that decreases interstitial cystitis symptoms but to our knowledge its mechanism of action is unknown. We investigated the effect of intravesical IPD-1151T on mediator release from bladder explants in experimental cystitis.

MATERIALS AND METHODS:

A catheter was inserted into the bladder of female mice. After urine was emptied normal saline, carbachol (100 nM) or lipopolysaccharide (10 mg/ml) was introduced with or without 10-minute pretreatment with IPD-1151T. Urine was removed after 45 minutes for histamine and tumor necrosis factor-alpha assays. The bladder was removed after 4 hours, minced into 1 mm2 pieces and cultured with or without triggers overnight for mediator release. The effect of IPD-1151T was also tested on rat skin vascular permeability as well as on purified rat peritoneal mast cells and human cord blood derived mast cells.

RESULTS:

Carbachol significantly increased histamine release in urine (61.3% in 8 preparations, p<0.05) but not in explant medium. IPD-1151T inhibited this effect by 77%. Lipopolysaccharide induced a 350% urine histamine increase in 9 preparations (p<0.05) and a 300% tumor necrosis factor-alpha increase in explant medium. IPD-1151T inhibited the lipopolysaccharide induced medium tumor necrosis factor-alpha increase by 95% in 5 preparations (p<0.05). IPD-1151T did not inhibit rat skin vascular permeability or purified rat peritoneal mast cell activation by compound 48/80 or human cord blood derived mast cells by anti-IgE.

CONCLUSIONS:

IPD-1151T inhibits bladder release of histamine and tumor necrosis factor-alpha through a mechanism that does not appear to involve direct mast cell inhibition. These findings may justify a beneficial effect of IPD-1151T in interstitial cystitis.

• Authors: W Boucher, D Kempuraj, J Cao, D Papaliodis, T C Theoharides
• Journal: The Journal of urology (J Urol) Vol. 177 Issue 3 Pg. 1186-90 (Mar 2007) ISSN: 0022-5347 [Print] United States
• PMID: 17296442 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Arylsulfonates
• Histamine Antagonists
• Sulfonium Compounds
• Tumor Necrosis Factor-alpha
• suplatast tosilate

Topics

• Administration, Intravesical
• Animals
• Arylsulfonates (administration & dosage, pharmacology)
• Capillary Permeability (drug effects)
• Cell Culture Techniques
• Cystitis, Interstitial (metabolism)
• Female
• Histamine Antagonists (administration & dosage, pharmacology)
• Histamine Release (drug effects)
• Humans
• Male
• Mast Cells (drug effects)
• Mice
• Mice, Inbred C57BL
• Rats
• Rats, Sprague-Dawley
• Skin (drug effects)
• Sulfonium Compounds (administration & dosage, pharmacology)
• Tumor Necrosis Factor-alpha (urine)