Schmidt C, Giese T, Goebel R, Schilling M, Marth T, Ruether A, Schreiber S, Zeuzem S, Meuer S C, Stallmach A
Department of Internal Medicine II, Saarland University, Homburg, Germany.
Int J Colorectal Dis. 2007 Sep;22(9):1013-20. doi: 10.1007/s00384-007-0282-2. Epub 2007 Feb 21.
It has been suggested that Crohn's Disease (CD) is associated with an elevated T helper 1 response as manifested by increased production of interleukin-18 (IL-18). Local concentrations of neutralizing IL-18 binding proteins (IL-18 bp) may counteract biological functions of mature IL-18 in mucosal inflammation. Therefore, we investigated the IL-18/IL-18 bp system in a large group of patients with active inflammatory bowel disease (IBD) to identify patients that could respond theoretically to IL-18 neutralizing treatment strategies.
PATIENT/METHODS: IL-18 and IL-18 bp messenger RNA (mRNA) expression in colonic mucosa from patients with active CD (n = 72), active ulcerative colitis (UC; n = 32), and non-IBD controls (infectious colitis or diverticulitis; n = 19) and normal, non-diseased controls (n = 20) were measured by reverse-transcribed real-time polymerase chain reaction. Mature IL-18 protein and IL-18 bp expression in inflamed mucosa were assessed by Western blotting.
RESULTS/FINDINGS: Although IL-18 mRNA was increased in some patients with CD, the increase was not statistically significant. Densitometric evaluation of IL-18/alpha-actin ratio in patients with active CD (n = 20) and patients with UC (n = 10) demonstrated an increased ratio of IL-18 protein in CD when compared to UC (1.04 vs 0.72 [median]). On closer inspections, only 7/20 CD patients had an increased IL-18 protein expression in inflamed areas compared to noninflamed mucosa.
INTERPRETATION/CONCLUSION: IL-18 expression in active CD is heterogeneous, only a minority of patients expresses elevated levels. Further treatment strategies targeting IL-18 expression in active CD should be concentrated on this subgroup of patients.
有人提出，克罗恩病（CD）与辅助性T细胞1反应增强有关，表现为白细胞介素18（IL-18）产生增加。局部中和性IL-18结合蛋白（IL-18 bp）的浓度可能会抵消成熟IL-18在黏膜炎症中的生物学功能。因此，我们在一大组活动性炎症性肠病（IBD）患者中研究了IL-18/IL-18 bp系统，以确定理论上可能对IL-18中和治疗策略有反应的患者。
患者/方法：通过逆转录实时聚合酶链反应测量活动性CD患者（n = 72）、活动性溃疡性结肠炎（UC；n = 32）、非IBD对照（感染性结肠炎或憩室炎；n = 19）以及正常非患病对照（n = 20）的结肠黏膜中IL-18和IL-18 bp信使核糖核酸（mRNA）的表达。通过蛋白质印迹法评估炎症黏膜中成熟IL-18蛋白和IL-18 bp的表达。
结果/发现：虽然部分CD患者的IL-18 mRNA有所增加，但这种增加无统计学意义。对20例活动性CD患者和10例UC患者的IL-18/α-肌动蛋白比率进行光密度分析，结果显示，与UC患者相比，CD患者的IL-18蛋白比率有所增加（中位数分别为1.04和0.72）。进一步检查发现，与非炎症黏膜相比，仅7/20的CD患者在炎症区域的IL-18蛋白表达增加。
解读/结论：活动性CD中IL-18的表达存在异质性，只有少数患者表达水平升高。针对活动性CD中IL-18表达的进一步治疗策略应集中于这一亚组患者。
