白细胞介素-23对炎症性肠病患者外周血自然杀伤细胞的免疫调节作用

目的 研究白细胞介素(IL)-23对炎症性肠病(IBD)患者外周血中自然杀伤(NK)细胞促炎细胞因子分泌和细胞毒作用的影响,探讨其在IBD发病中的意义.方法 利用免疫磁珠分离12名健康人、16例克罗恩病(CD)患者和25例溃疡性结肠炎(UC)患者外周血NK细胞.体外培养NK细胞,并予空白刺激、IL-23刺激、IgG刺激或IL-23+IgG联合刺激.酶联免疫吸附试验法检测细胞培养上清中肿瘤坏死因子(TNF)-αa和干扰素(IFN)-γ分泌水平.流式细胞仪检测经不同刺激培养的NK细胞对K562细胞的细胞毒作用.结果 正常对照组的NK细胞经人IgG和IL-23单独刺激后TNF-α、IFN-γ的分泌水平未明显增高(P值均＞0.05),二者联合刺激则能显著促进TNF-α、IFN-γ分泌(P值均＜0.05).单独应用IgG刺激CD和UC患者NK细胞分泌TNF-α、IFN-γ的效果不明显(P值均＞0.05).单独应用IL-23则具刺激作用(P值均＜0.05),二者联合应用的刺激作用更明显(P值均＜0.01).IL-23单独刺激和联合刺激均不能增强正常对照组NK细胞的细胞毒作用(P值均＞0.05).但单独应用IL-23可增强UC和CD患者NK细胞的细胞毒作用(分别为51.5%±7.1%和50.2%±8.7%,P值均＜0.05),且联合刺激可进一步增强该作用(分别为65.3%±6.6%和62.4%±5.5%,P值均＜0.01).结论 IL-23能刺激IBD患者NK细胞分泌TNF-α和IFN-γ,并能增强NK细胞的细胞毒作用,可能直接参与了IBD的发病过程.

Immune regulation of interleukin-23 on peripheral blood natural killer cell in patients with inflammatory bowel disease

Objective To study the potential role of interleukin-23(IL-23)in induction of peripheral blood natural killer(NK)cell activation and cytotoxicity in patients with inflammatory bowel disease(IBD),and to investigate its clinical relevance to the pathogenesis.Methods Peripheral blood was collected from 12 healthy subjects,16 patients with Crohn's disease(CD)and 25 patients with ulcerative colitis(UC).NK cells isolated from peripheral blood using immunomagnetie beads were cultured in vitro and stimulated with IL-23 or IgG,or combination of two.Concentrations of tumor necrosis factor α(TNF-α)and interferon-γ(IFN-γ)were determined by enzyme linked immunosorbent assay.NK eytotoxicity to K562 cell was detected by flow cytometry.Results The levels of TNF-α and IFN-γ were not increased in healthy controls under stimulation with IgG or IL-23 (P＞0.05),but they were elevated under stimulation with IgG plus IL-23(P＜0.05).IL-23,not IgG,was found tO enhance TNF-α and IFN-γ secretion in IBD patients(P＜0.05).The levels of TNF-α and IFN-γ were significantly increased in IBD patients under the stimulation of IL-23 plus lgG (P＜0.01).The cytotoxicity of NK cells in healthy controls was not observed under stimulation with IL-23 alone or IL-23 plus IgG,whereas it could be enhanced by stimulation with IL-23 in CD patients (62.4%±5.5%)and UC patients(65.3%±6.6%,P＜0.05)or with IL-23 plus IgG in CD patients (50.2%±8.7%)and UC patients(51.5%±7.1%,P＜0.01).ConclusionIL-23 plays an important role in induction of NK cell activation and cytotoxicity in IBD patients,and may be involved in development of IBD.