Matsuda Reikei, Koide Tomoko, Tokoro Chikako, Yamamoto Tsuyoshi, Godai Ten'i, Morohashi Taiki, Fujita Yuji, Takahashi Daisuke, Kawana Ichiro, Suzuki Shinichiro, Umemura Satoshi
Department of Internal Medicine, Fujisawa Shounandai Hospital, Fujisawa, Kanagawa, Japan.
Inflamm Bowel Dis. 2009 Mar;15(3):328-34. doi: 10.1002/ibd.20759.
Cytokines have validated roles in the immunopathogenesis of inflammatory bowel disease (IBD). This study was to investigate the expressions of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-8, and IL-10 mRNAs in the colonic mucosa of patients with ulcerative colitis (UC) during active and quiescent UC.
At colonoscopy, biopsies were taken from inflamed and non-inflamed mucosa of patients with steroid-naive UC (n = 15), non-IBD inflammatory colitis controls (ICC, n = 6), and non-colitis controls (NCC, n = 14). The presence of extensive mononuclear cells and neutrophils infiltrate in the lamina propria, cryptitis, and epithelial damage defined an inflammatory lesion in the mucosa. Quantitative cytokine mRNA expressions in biopsies were measured by real-time polymerase chain reaction (PCR).
Of 15 UC patients, 3 remitted with 5-aminosalicylate and 11 received granulocytapheresis; of these, 10 remitted. At baseline, IL-6, IL-8, TNF-alpha, and IL-10 mRNAs were high in inflamed mucosa compared with NCC (P < 0.01). In active UC, IL-6, IL-8 and IL-10 mRNAs were high compared with non-inflamed mucosa (P = 0.03, P = 0.03, P < 0.05, respectively). Both TNF-alpha mRNA (P = 0.03) and IL-6 mRNA (P = 0.04) were higher in UC compared with ICC. Even in non-inflamed mucosa, IL-8 and TNF-alpha mRNA expressions were high compared with NCC. Both IL-6 and IL-8 mRNAs decreased to normal levels after granulocytapheresis.
During active UC, all 4 cytokine mRNA levels were high; only IL-6 and IL-8 mRNAs decreased to normal levels during remission. IL-8 mRNA was high even at sites of endoscopically quiescent UC during active disease. Steroid naïve patients respond well to granulocytapheresis.
细胞因子在炎症性肠病(IBD)的免疫发病机制中具有已被证实的作用。本研究旨在调查溃疡性结肠炎(UC)患者在活动期和缓解期结肠黏膜中肿瘤坏死因子(TNF)-α、白细胞介素(IL)-6、IL-8和IL-10 mRNA的表达情况。
在结肠镜检查时,从初治UC患者(n = 15)、非IBD炎症性结肠炎对照组(ICC,n = 6)和非结肠炎对照组(NCC,n = 14)的炎症和非炎症黏膜中获取活检组织。固有层中广泛的单核细胞和中性粒细胞浸润、隐窝炎和上皮损伤的存在定义了黏膜中的炎症病变。通过实时聚合酶链反应(PCR)测量活检组织中细胞因子mRNA的定量表达。
15例UC患者中,3例用5-氨基水杨酸缓解,11例接受粒细胞单采术;其中,10例缓解。在基线时,与NCC相比,炎症黏膜中IL-6、IL-8、TNF-α和IL-10 mRNA水平较高(P < 0.01)。在活动期UC中,与非炎症黏膜相比,IL-6、IL-8和IL-10 mRNA水平较高(分别为P = 0.03、P = 0.03、P < 0.05)。与ICC相比,UC中TNF-α mRNA(P = 0.03)和IL-6 mRNA(P = 0.04)均较高。即使在非炎症黏膜中,与NCC相比,IL-8和TNF-α mRNA表达也较高。粒细胞单采术后,IL-6和IL-8 mRNA均降至正常水平。
在活动期UC期间,所有4种细胞因子mRNA水平均较高;缓解期只有IL-6和IL-8 mRNA降至正常水平。在活动期疾病期间,即使在内镜检查静止的UC部位,IL-8 mRNA也较高。初治患者对粒细胞单采术反应良好。