膀胱内注射托西酸舒拉他定（IPD-1151T）可抑制实验性膀胱炎症。

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

作者信息

Boucher W, Kempuraj D, Cao J, Papaliodis D, Theoharides T C

机构信息

Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine and Tufts-New England Medical Center, Boston, Massachusetts 02111, USA.

出版信息

J Urol. 2007 Mar;177(3):1186-90. doi: 10.1016/j.juro.2006.10.036.

DOI:10.1016/j.juro.2006.10.036

PMID:17296442

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.

摘要

目的

间质性膀胱炎是一种以尿急、尿频和炎症变化不定为特征的膀胱疼痛性疾病，但尚无治愈性疗法。托西酸舒拉他定（IPD - 1151T）是一种免疫调节化合物，可减轻间质性膀胱炎症状，但据我们所知，其作用机制尚不清楚。我们研究了膀胱内注射IPD - 1151T对实验性膀胱炎中膀胱外植体介质释放的影响。

材料与方法

将导管插入雌性小鼠膀胱。排空尿液后，在有或没有用IPD - 1151T预处理10分钟的情况下，注入生理盐水、卡巴胆碱（100 nM）或脂多糖（10 mg/ml）。45分钟后收集尿液进行组胺和肿瘤坏死因子-α检测。4小时后取出膀胱，切成1平方毫米的小块，在有或没有刺激物的情况下培养过夜以检测介质释放。还测试了IPD - 1151T对大鼠皮肤血管通透性以及纯化的大鼠腹膜肥大细胞和人脐血来源肥大细胞的影响。

结果

卡巴胆碱显著增加尿液中组胺释放（8份标本中增加61.3%，p<0.05），但在外植体培养基中未增加。IPD - 1151T可将此作用抑制77%。脂多糖在9份标本中使尿液组胺增加350%（p<0.05），在外植体培养基中使肿瘤坏死因子-α增加300%。在5份标本中，IPD - 1151T可将脂多糖诱导的培养基中肿瘤坏死因子-α增加抑制95%（p<0.05）。IPD - 1151T不抑制大鼠皮肤血管通透性，也不抑制化合物48/80诱导的纯化大鼠腹膜肥大细胞活化或抗IgE诱导的人脐血来源肥大细胞活化。