克罗恩病的不完全性急性炎症:一项临床调查  

Defective acute inflammation in Crohn's disease: A clinical investigation

作　　者：Marks D. J. Harbord M. W. MacAllister R. A.W. Segal 陈云茹(译) 史敏(校) 

机构地区：[1]不详 [2]Department of Medicine, University College London, London WC1E 6JJ, United Kingdom

出　　处：《世界核心医学期刊文摘（胃肠病学分册）》2006年第8期2-3,共2页Core Journals in Gastroenterology

摘　　要：Background: The cause of Crohn’s disease has not been mechanistically proven. We tested the hypothesis that the disease is a form of immunodeficiency caused by impaired innate immunity. Methods: We investigated inflammatory responses in patients and controls by quantifying neutrophil recruitment and cytokine production after acute trauma, interleukin 8 secretion by cultured monocyte-derived macrophages after exposure to inflammatory mediators, and local inflammatory and vascular changes in response to subcutaneous injection of heat-killed Escherichia coli. Findings: In patients with Crohn’s disease, trauma to rectum, ileum, or skin led to abnormally low neutrophil accumulation (differences from healthy individuals of 79% , n = 8, p =0.0003; 57%, n = 3, p=0.05; 50%, n = 13, p< 0.0001, respectively) and lower production of proinflammatory interleukin 8 (63%, n=7, p= 0.003; 63%, n = 3, p = 0.05; 45%, n = 8, p< 0.0001) and interleukin 1β (50%, n = 8, p =0.0005). Interleukin 8 secretion by cultured macrophages was reduced after exposure to acute wound fluid (38%, n =50, p < 0. 0001), C5a (48%, n=41, p = 0.0005), or tumour necrosis factor α (52%, n = 27, p < 0. 0001). Local inflammatory reaction to inoculation with E coli was attenuated, as quantified by changes in bloodflow (ileal disease 50%, n = 6, p = 0. 01; colonic disease 77%, n=6, p=0.0003).This response was mediated by nitric oxide in controls, was increased by sildenafil in patients, and was not related to CARD15 genotype. Interpretation: In Crohn’s disease, a constitutionally weak immune response predisposes to accumulation of intestinal contents that breach the mucosal barrier of the bowel wall, resulting in granuloma formation and chronic inflammation. Polymorphisms in CARD15 do not underlie this phenotype, but incapacitate the NOD2 pathway that can compensate for impairment of innate inflammation. Current treatment of secondary chronic inflammation might exaggerate the underlying lesion and promote chronic disease.Background： The cause of Crohn＇s disease has not been mechanistically proven. We tested the hypothesis that the disease is a form of immunodeficiency caused by impaired innate immunity. Methods： We investigated inflammatory responses in patients and controls by quantifying neutrophil recruitment and cytokine production after acute trauma, interleukin 8 secretion by cultured monocyte-derived macrophages after exposure to inflammatory mediators, and local inflammatory and vascular changes in response to subcutaneous injection of heat-killed Escherichia coli. Findings： In patients with Crohn＇s disease, trauma to rectum, ileum, or skin led to abnormally low neutrophil accumulation （differences from healthy individuals of 79%, n=8, p=0. 0003; 57%, n=3, p=0.05; 50%, n= 13, p 〈 0. 0001, respectively） and lower production of proinflammatory interleukin 8 （63%, n = 7, p = 0. 003; 63%, n=3, p=0.05; 45%, n=8, p〈0.0001） and interleukin 113 （50%, n =8, p =0. 0005）. Interleukin 8 secretion by cultured macrophages was reduced after exposure to acute wound fluid （38%, n = 50, p 〈 0. 0001）, C5a （48%, n=41, p=0.0005）, or tumour necrosis factor α （52%, n = 27, p 〈 0. 0001 ）. Local inflammatory reaction to inoculation with E coli was attenuated, as quantified by changes in bloodflow （ileal disease 50%, n = 6, p = 0.01; colonic disease 77%, n = 6, p = 0. 0003） .This response was mediated by nitric oxide in controls, was increased by sildenafil in patients, and was not related to CARD15 genotype.

关 键 词：克罗恩病 急性炎症 临床调查 不完全性 中性粒细胞聚集 细胞因子产物 单核细胞衍生 操作特征分析 白介素-8 免疫缺陷 

分 类 号：R574.62[医药卫生—消化系统] R285.5[医药卫生—内科学]