Hölttä Veera, Sipponen Taina, Westerholm-Ormio Mia, Salo Harri M, Kolho Kaija-Leena, Färkkilä Martti, Savilahti Erkki, Vaarala Outi, Klemetti Paula
Immune Response Unit, Department of Vaccination and Immune Protection, National Institute for Health and Welfare, Haartmaninkatu 8, 00290 Helsinki, Finland.
ISRN Gastroenterol. 2012;2012:505432. doi: 10.5402/2012/505432. Epub 2012 Jun 14.
Aim. In Crohn's disease (CD), anti-TNF-α treatment is a potent medication. We aimed to characterize the effect of anti-TNF-α treatment on T effector and regulatory cells. Material and Methods. We studied T-effector and regulatory cells on cellular and mRNA levels in intestinal biopsy samples from 13 Crohn's disease patient. Biopsies were obtained at baseline and 3 months after anti-TNF-α treatment, and from 14 inflammation-free control subjects. Results. Patients had higher numbers of ileal IL-17(+) and forkhead box P3 (FOXP3)(+) cells than did control subjects, both before ( P ≤ 0.001 and P ≤ 0.05, resp.) and after the anti-TNF-α treatment (P ≤ 0.01, P ≤ 0.01). Intestinal interferon-γ and IL-17 mRNA expression was higher in Crohn's disease and remained elevated after anti-TNF-α treatment. The ratio of IL-17(+) cells to CD4(+) cells decreased (P ≤ 0.05) and compared to baseline the ratio of IL-17(+) cells to FOXP3(+) was lower after treatment (P ≤ 0.05). Conclusions. TNF-α-blocking agents improved intestinal balance between IL-17(+) T-effector and regulatory T cells, although intestinal IL-17 upregulation remained elevated.
目的。在克罗恩病(CD)中,抗TNF-α治疗是一种有效的药物。我们旨在描述抗TNF-α治疗对T效应细胞和调节性细胞的影响。材料与方法。我们在细胞和mRNA水平上研究了13例克罗恩病患者肠道活检样本中的T效应细胞和调节性细胞。活检样本在基线时以及抗TNF-α治疗3个月后获取,同时还获取了14名无炎症对照受试者的样本。结果。患者回肠中IL-17(+)和叉头框P3(FOXP3)(+)细胞数量在抗TNF-α治疗前(分别为P≤0.001和P≤0.05)和治疗后(P≤0.01,P≤0.01)均高于对照受试者。克罗恩病患者肠道中干扰素-γ和IL-17 mRNA表达较高,并且在抗TNF-α治疗后仍保持升高。IL-17(+)细胞与CD4(+)细胞的比例降低(P≤0.05),与基线相比,治疗后IL-17(+)细胞与FOXP3(+)细胞的比例更低(P≤0.05)。结论。TNF-α阻断剂改善了肠道中IL-17(+) T效应细胞和调节性T细胞之间的平衡,尽管肠道IL-17上调仍保持升高。