监测儿童糖皮质激素治疗效果的新方法。

New means to monitor the effect of glucocorticoid therapy in children.

机构信息

Division of Gastroenterology, Hospital for Children and Adolescents, University of Helsinki, Box 281, Helsinki, FIN-00029, Finland.

出版信息

World J Gastroenterol. 2010 Mar 7;16(9):1104-9. doi: 10.3748/wjg.v16.i9.1104.

DOI:10.3748/wjg.v16.i9.1104

PMID:20205281

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2835787/

Abstract

AIM

To study the individual effects of glucocorticoid (GC) therapy on the state of immune activation in patient serum.

METHODS

We developed a novel assay in which the effect of corticosteroid-treated patient serum on healthy donor peripheral blood mononuclear cells (target cells) was studied, with a panel of markers for effector [interferon (IFN)gamma and interleukin (IL)-5] and regulatory T cells (FOXP3 and glucocorticoid-induced tumor necrosis factor receptor, GITR). The study group comprised 19 children with inflammatory bowel disease. The individual effect of patient serum on target cells was analyzed prior to GC therapy and 2 wk later.

RESULTS

The effect of GC therapy mediated by patient serum was seen as a decrease in the target cells expression of regulatory T-cell-related markers GITR (median suppression 24%, range of suppression 1%-63%, in 2 cases increase of 6% and 77%, P < 0.01 for mitogen-activated target cells) and FOXP3 (median suppression 33%, range of suppression 0%-79%, in one case an increase of 173%, P < 0.05 for resting cells), and secretion of IFNgamma [from a mean of 87 700 pg/mL (SD 33 900 pg/mL) to 60 900 pg/mL (SD 44 200 pg/mL) in mitogen-activated target cells, 13 of the cases showed a decrease, P < 0.01]. The total or weight-related prednisolone dose did not correlate with the patient-serum-induced changes in the target cell markers.

CONCLUSION

GC response could be monitored at an individual level by studying the effect of patient serum on signaling pathways of target immune cells.

摘要

目的

研究糖皮质激素（GC）治疗对患者血清中免疫激活状态的个体影响。

方法

我们开发了一种新的检测方法，研究了皮质类固醇治疗患者血清对健康供体外周血单个核细胞（靶细胞）的影响，使用了一系列效应[干扰素（IFN）γ和白细胞介素（IL）-5]和调节性 T 细胞（FOXP3 和糖皮质激素诱导的肿瘤坏死因子受体，GITR）的标志物。研究组包括 19 例炎症性肠病患儿。在 GC 治疗前和 2 周后分析患者血清对靶细胞的个体影响。

结果

GC 治疗介导的患者血清对靶细胞的作用表现为调节性 T 细胞相关标志物 GITR（抑制中位数 24%，抑制范围 1%-63%，2 例增加 6%和 77%，对有丝分裂原激活的靶细胞 P<0.01）和 FOXP3（抑制中位数 33%，抑制范围 0%-79%，1 例增加 173%，对静止细胞 P<0.05）的表达和 IFNγ的分泌[从平均 87700pg/mL（SD 33900pg/mL）到有丝分裂原激活的靶细胞中的 60900pg/mL（SD 44200pg/mL），13 例下降，P<0.01]。总或体重相关的泼尼松龙剂量与患者血清诱导的靶细胞标志物变化无关。