Department of Gastroenterology, Academic Medical Center, Amsterdam, The Netherlands.
Gut. 2010 Sep;59(9):1213-21. doi: 10.1136/gut.2010.213108. Epub 2010 Jul 21.
Mast cell activation is thought to be involved in visceral hypersensitivity, one of the main characteristics of the irritable bowel syndrome (IBS). A study was therefore undertaken to investigate the effect of the mast cell stabiliser ketotifen on rectal sensitivity and symptoms in patients with IBS.
60 patients with IBS underwent a barostat study to assess rectal sensitivity before and after 8 weeks of treatment. After the initial barostat, patients were randomised to receive ketotifen or placebo. IBS symptoms and health-related quality of life were scored. In addition, mast cells were quantified and spontaneous release of tryptase and histamine was determined in rectal biopsies and compared with biopsies from 22 age- and gender-matched healthy volunteers.
Ketotifen but not placebo increased the threshold for discomfort in patients with IBS with visceral hypersensitivity. This effect was not observed in normosensitive patients with IBS. Ketotifen significantly decreased abdominal pain and other IBS symptoms and improved quality of life. The number of mast cells in rectal biopsies and spontaneous release of tryptase were lower in patients with IBS than in healthy volunteers. Spontaneous release of histamine was mostly undetectable but was slightly increased in patients with IBS compared with healthy volunteers. Histamine and tryptase release were not altered by ketotifen.
This study shows that ketotifen increases the threshold for discomfort in patients with IBS with visceral hypersensitivity, reduces IBS symptoms and improves health-related quality of life. Whether this effect is secondary to the mast cell stabilising properties of ketotifen or H(1) receptor antagonism remains to be further investigated. Trial Registration Number NTR39, ISRCTN22504486.
肥大细胞活化被认为与内脏高敏有关，这是肠易激综合征（IBS）的主要特征之一。因此，进行了一项研究，以调查肥大细胞稳定剂酮替芬对 IBS 患者直肠敏感性和症状的影响。
60 例 IBS 患者接受直肠测压检查，以评估治疗前和治疗 8 周后的直肠敏感性。初始测压后，患者随机接受酮替芬或安慰剂治疗。评估 IBS 症状和健康相关生活质量。此外，定量直肠活检中的肥大细胞，并比较 IBS 患者和 22 名年龄和性别匹配的健康志愿者的活检中组织蛋白酶和组胺的自发释放。
酮替芬而非安慰剂可增加内脏高敏性 IBS 患者的不适阈值。在无内脏高敏性的 IBS 患者中未观察到这种作用。酮替芬可显著减轻腹痛和其他 IBS 症状，并改善生活质量。直肠活检中的肥大细胞数量和组织蛋白酶的自发释放均低于健康志愿者。组胺的自发释放大多不可检测，但与健康志愿者相比，IBS 患者略有增加。酮替芬未改变组胺和组织蛋白酶的释放。
本研究表明，酮替芬可增加内脏高敏性 IBS 患者的不适阈值，减轻 IBS 症状并改善健康相关生活质量。这种作用是否继发于酮替芬的肥大细胞稳定作用或 H1 受体拮抗作用，尚需进一步研究。试验注册号 NTR39，ISRCTN22504486。
