Ruffolo Cesare, Scarpa Marco, Faggian Diego, Pozza Anna, Navaglia Filippo, D'Incà Renata, Hoxha Pranvera, Romanato Giovanna, Polese Lino, Sturniolo Giacomo Carlo, Plebani Mario, D'Amico Davide Francesco, Angriman Imerio
Clinica Chirurgica 1, Department of Surgical and Gastroenterological Sciences, University of Padua, Padova, Italy.
Inflamm Bowel Dis. 2008 Oct;14(10):1406-12. doi: 10.1002/ibd.20486.
Nowadays anti-TNF-alpha antibodies are used for the treatment of perianal Crohn's disease (CD). Nevertheless, this treatment is effective in only a part of these patients and recent studies suggested a role for other cytokines in chronic bowel inflammation. The aim of this study was to assess the cytokine profile in the rectal mucosa of patients affected by perianal CD and to understand its relations with the systemic cytokine profile and inflammatory parameters and the need for surgery.
Seventeen patients affected by perianal CD, 7 affected by CD without perianal involvement, and 17 healthy controls were enrolled and underwent blood sampling and endoscopy. During endoscopy rectal mucosal samples were taken and the expression of TNF-alpha, IL-6, IL-1 beta, IL-12, and TGF-beta1 was quantified with enzyme-linked immunosorbent assay (ELISA). Local cytokine levels were compared and correlated with diagnosis, therapy, phenotype (fistulizing and stenosing), and disease activity parameters.
In the group with perianal CD, rectal mucosal IL-1 beta, IL-6, and serum IL-6 and TNF-alpha were higher than in patients with small bowel CD and healthy controls. IL-12 and TGF-beta1 mucosal levels did not show any differences among the 3 groups. Mucosal IL-6 significantly correlated with the Perianal Crohn's Disease Activity Index and mucosal TNF-alpha and IL-1 beta. Mucosal TNF-alpha and IL-1 beta showed a direct correlation with the histological grade of disease activity.
The cytokines network analysis in perianal CD shows the important involvement of IL-1 beta, IL-6, and TNF-alpha. Furthermore, mucosal levels of IL-6 and IL-12 are predictors of recurrence and of need for surgery in perianal CD patients.
如今，抗肿瘤坏死因子-α（TNF-α）抗体被用于治疗肛周克罗恩病（CD）。然而，这种治疗仅对部分此类患者有效，并且最近的研究表明其他细胞因子在慢性肠道炎症中发挥作用。本研究的目的是评估肛周CD患者直肠黏膜中的细胞因子谱，并了解其与全身细胞因子谱、炎症参数以及手术需求之间的关系。
纳入17例肛周CD患者、7例无肛周受累的CD患者以及17名健康对照者，进行血液采样和内镜检查。在内镜检查过程中采集直肠黏膜样本，并用酶联免疫吸附测定（ELISA）对TNF-α、白细胞介素-6（IL-6）、白细胞介素-1β（IL-1β）、白细胞介素-12（IL-12）和转化生长因子-β1（TGF-β1）的表达进行定量。比较局部细胞因子水平，并将其与诊断、治疗、表型（瘘管形成和狭窄）以及疾病活动参数相关联。
在肛周CD组中，直肠黏膜IL-1β、IL-6以及血清IL-6和TNF-α高于小肠CD患者和健康对照者。IL-12和TGF-β1的黏膜水平在三组之间未显示出任何差异。黏膜IL-6与肛周克罗恩病活动指数、黏膜TNF-α和IL-1β显著相关。黏膜TNF-α和IL-1β与疾病活动的组织学分级呈直接相关。
肛周CD中的细胞因子网络分析显示IL-1β、IL-6和TNF-α有重要参与。此外，IL-6和IL-12的黏膜水平是肛周CD患者复发和手术需求的预测指标。
