Frieri G, Giacomelli R, Pimpo M, Palumbo G, Passacantando A, Pantaleoni G, Caprilli R
Cattedra di Gastroenterologia, Università di L'Aquila, L'Aquila, Italy.
Gut. 2000 Sep;47(3):410-4. doi: 10.1136/gut.47.3.410.
The treatment of ulcerative colitis (UC) with 5-aminosalicylic acid (5-ASA) does not have the same therapeutic effect in all patients. We tested the hypothesis that the effectiveness of the drug is related to its mucosal concentration.
Twenty one UC patients receiving oral 5-ASA (2.4-3.2 g/day) were enrolled in the study. Four were also receiving topical treatment (2 g/day).
Six endoscopic biopsies were taken from the rectum for measurement of 5-ASA concentrations (ng/mg) by HPLC; soluble interleukin 2 receptor (sIL-2R) concentrations (U/ml) were measured by ELISA and histology. Endoscopic and histological appearance was graded on a four point scale (0-3). The Wilcoxon's rank test and Pearson's correlation coefficient were used for statistical analysis.
Mucosal concentrations of 5-ASA were significantly higher (p=0.03) in patients with endoscopic scores of 0-1 compared with those with scores of 2-3 (16.1 (range 10.2-45) v 5. 5 (3.5-17.4), respectively) and in patients with lower histological inflammation compared with those with more severe scores (17.4 (10. 5-45) v 8.9 (3.5-17.2), respectively) (p<0.01). In contrast, mucosal sIL2-R concentrations were significantly lower in patients with slight endoscopic and histological lesions than in those with more severe disease. A significative inverse correlation (r=-0.85) was found between 5-ASA and sIL-2R mucosal concentrations (p=0.00008).
In patients with UC, in the same area of the intestinal tract, we found that the higher the 5-ASA mucosal concentrations, the lower the IL-2R levels and endoscopic and histological scores. We hypothesise that maintenance of high mucosal 5-ASA concentrations in all colonic segments could contribute to improve clinical outcome in UC patients.
5-氨基水杨酸（5-ASA）治疗溃疡性结肠炎（UC）并非对所有患者都有相同的治疗效果。我们检验了该药物疗效与其黏膜浓度相关的假说。
21例接受口服5-ASA（2.4 - 3.2克/天）的UC患者纳入本研究。4例同时接受局部治疗（2克/天）。
从直肠取6块内镜活检组织，用高效液相色谱法（HPLC）测定5-ASA浓度（纳克/毫克）；用酶联免疫吸附测定法（ELISA）和组织学方法测定可溶性白细胞介素2受体（sIL-2R）浓度（单位/毫升）。内镜和组织学表现按四点量表（0 - 3）分级。采用威尔科克森秩和检验及皮尔逊相关系数进行统计分析。
内镜评分为0 - 1分的患者5-ASA黏膜浓度显著高于评分为2 - 3分的患者（分别为16.1（范围10.2 - 45）对5.5（3.5 - 17.4），p = 0.03），组织学炎症较轻的患者5-ASA黏膜浓度高于炎症较重的患者（分别为17.4（10.5 - 45）对8.9（3.5 - 17.2），p < 0.01）。相反，内镜和组织学病变轻微的患者黏膜sIL-2R浓度显著低于病变较严重的患者。5-ASA与sIL-2R黏膜浓度之间存在显著负相关（r = -0.85）（p = 0.00008）。
在UC患者的肠道同一区域，我们发现5-ASA黏膜浓度越高，IL-2R水平以及内镜和组织学评分越低。我们推测在所有结肠段维持高黏膜5-ASA浓度可能有助于改善UC患者的临床结局。
