School of Public Health, University of California, Berkeley, CA, USA.
J Pediatr Gastroenterol Nutr. 2012 Jun;54(6):769-75. doi: 10.1097/MPG.0b013e3182455bb3.
Increasing evidence suggests that cytokine dysregulation in T-helper 1 and T-helper 2 (TH1/TH2) subsets contributes to the pathogenesis of Crohn disease (CD). The present pilot study examines the hypothesis that cytokine profiles differ between pediatric and adult patients with CD.
Production of TH1 cytokines interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) and of TH2 cytokines interleukin-4 (IL-4) and IL-6 was analyzed in peripheral blood of patients with CD and healthy controls (n=20) using flow cytometry after in vitro stimulation.
In both pediatric and adult subjects, frequencies of TNF-α CD4+ T cells were higher in patients with CD than in controls (P=0.009 and P=0.047, respectively). Percentages of cells expressing IL-4 were slightly increased (P=0.036), whereas those for IFN-γ were decreased (P=0.009) in pediatric patients with CD compared with controls. As expected, the overall production of TH1 cytokines was higher in adults compared with pediatric subjects. When memory CD4+CD45RO+ T cells were considered, lower IFN-γ expression was observed in pediatric subjects with CD compared with controls (P=0.009), matching the trend seen in the general CD4+ T cell population. The percentage of CD4+CD45RO+ T cells was increased in adult patients with CD compared with pediatric patients with CD (P=0.016).
The present study describes a peripheral blood TH1/TH2 cytokine imbalance in CD and suggests different immunological mechanisms in children and adults for disease pathogenesis.
越来越多的证据表明,辅助性 T 细胞 1(TH1)和辅助性 T 细胞 2(TH2)亚群中的细胞因子失调导致克罗恩病(CD)的发病机制。本初步研究检验了这样一个假设,即 CD 患儿和成年患者的细胞因子谱存在差异。
采用流式细胞术检测经体外刺激后,CD 患儿和健康对照者(n=20)外周血中 TH1 细胞因子干扰素-γ(IFN-γ)和肿瘤坏死因子-α(TNF-α)以及 TH2 细胞因子白细胞介素-4(IL-4)和白细胞介素-6(IL-6)的产生情况。
在儿科和成年患者中,CD 患者的 TNF-α+CD4+T 细胞频率均高于对照组(P=0.009 和 P=0.047)。与对照组相比,CD 患儿的 IL-4 细胞表达百分比略有增加(P=0.036),而 IFN-γ 细胞表达百分比降低(P=0.009)。与儿科患者相比,成人患者的 TH1 细胞因子总产生量更高,这是预期的结果。当考虑记忆性 CD4+CD45RO+T 细胞时,与对照组相比,CD 患儿的 IFN-γ 表达明显降低(P=0.009),与 CD4+T 细胞总体群中观察到的趋势一致。与儿科 CD 患者相比,成年 CD 患者的 CD4+CD45RO+T 细胞百分比增加(P=0.016)。
本研究描述了 CD 患者外周血中 TH1/TH2 细胞因子失衡,并提示儿童和成人疾病发病机制中存在不同的免疫机制。