长效干扰素对克罗恩病患者肠黏膜白细胞介素-12、白细胞介素-17、肿瘤坏死因子-α和γ干扰素的影响

Effects of long-acting interferon on the expression of IL-12,IL-17,TNF-αand IFN-γin the intestinal mucosa of Crohn’s disease patients

目的探讨长效干扰素治疗克罗恩病(Crohn’s disease,CD)的免疫学机制,为其治疗CD提供一定的实验基础及理论依据。方法选取中南大学湘雅医院2015年6月至2016年6月门诊和病房确诊的16例CD患者的内镜活检标本,实验设CD治疗前、CD治疗后(长效干扰素10μg,肌注,2次/周,治疗4周)及正常对照组。正常对照组选取16例为结肠息肉患者,用免疫组织化学方法检测局部肠黏膜细胞因子白细胞介素(interleukin,IL)-12、IL-17、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)和γ干扰素(interferon-γ,IFN-γ)的表达。结果治疗前CD患者结肠组织中IL-12、IL-17、TNF-α和IFN-γ表达显著增多,结肠组织中IL-12、IL-17呈弥散性分布,在黏膜上皮均有表达,主要分布于黏膜腺体内及间质炎性细胞胞质;TNF-α仅在黏膜层间质表达,围绕炎性细胞核呈团块状的胞质表达;IFN-γ分布于肠黏膜固有层,腺体周围淋巴细胞膜表面。长效干扰素可降低CD患者结肠黏膜中IL-12、IL-17、TNF-α、IFN-γ。结论IL-12、IL-17、TNF-α和IFN-γ等促炎性细胞因子在CD黏膜免疫发生过程中发挥重要作用;长效干扰素能下调CD患者肠黏膜中IL-12、IL-17、TNF-α、IFN-γ的表达,具有治疗作用。

Objective To observe the effect of long-acting interferon on the expression of interleukin(IL)-12,IL-17,tumor necrosis factor-α(TNF-α)and interferon-γ(IFN-γ)in colonic mucosa of patients with Crohn’s disease(CD).Methods Collected intestinal mucosa specimens from 16 CD patients,the experiment was divided into three groups:before CD treatment,after CD treatment(long-acting interferon 10μg,intramuscular injection,twice one week,treatment for 4 weeks)and normal control group.IL-12,IL-17,TNF-αand IFN-γprotein expression were detected before and after long-acting interferon treatment.16 cases colon polyps were collected as the control group.Results The expressions of IL-12,IL-17,TNF-αand IFN-γin colonic mucosa had increased in CD.IL-12 and IL-17 were distributed diffusely in colon tissue,expressed in mucosal epithelium,mainly distributed in mucosal glands and interstitial inflammatory cell cytoplasm;TNF-αwas only expressed in the stroma of mucosal layer,and was expressed in the cytoplasm around the inflammatory nucleus.IFN-γwas distributed in the lamina propria of intestinal mucosa and on the surface of lymphocyte membrane around glands.After treatment,expressions of IL-12,IL-17,TNF-αand IFN-γin colonic mucosa had decreased in CD.Conclusion IL-12,IL-17,TNF-αand IFN-γplay an important role in the process of CD mucosal immunity,long-acting interferon can ajust immunization anti-inflammatory,this maybe the mechanism for its treatmentof CD.