Systemic bias of cytokine production toward cell-mediated immune regulation in IDDM and toward humoral immunity in Graves' disease
Systemic bias of cytokine production toward cell-mediated immune regulation in IDDM and toward humoral immunity in Graves' disease
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DOI：
10.2337/diabetes.46.2.237
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发表时间：
1997-02-01
期刊：
影响因子：
7.7
通讯作者：
Kolb, H
中科院分区：
文献类型：
--
作者：
Kallmann, BA;Huther, M;Kolb, H
紊乱的免疫调节被认为在IDDM和其他自身免疫性或过敏性疾病的发病机制中至关重要。因此，我们通过研究植物血凝素刺激的全血培养，验证了与健康对照者相比，新近发病的IDDM或Graves病患者的外周免疫系统普遍偏倚的假设。IDDM患者（n = 53）细胞产生的Th1细胞因子γ -干扰素（ifn - γ） （P = 0.028）和肿瘤坏死因子α (tnf - α) （P = 0.007）明显高于正常对照组（n = 56），而Th2细胞因子（白细胞介素[IL]-4， IL-10）水平相似。IDDM患者低水平的胰岛细胞抗体（ICAs）与高水平的Th1和Th2细胞因子相关。GAD抗体、ICA512抗体或胰岛素抗体与个体细胞因子谱无关。此外，HLA-DQ类型与Th1或Th2细胞因子的产生没有显著相关性。相反，格雷夫斯病患者（n = 18）的全血培养产生的tnf - α和IL-4明显低于正常受试者（P = 0.001-0.006）。然而，当分析个体中Th1和Th2细胞因子产生的平衡时，IDDM患者中ifn - γ或tnf - α与IL-4或IL-10的比值明显偏向Th1反应性（P = 0.0001），而Graves病中Th2细胞因子产生占优势（P = 0.0001）。反调节细胞因子的比例似乎是个体疾病过程中最可靠的标志。这项研究首次提供了人类免疫调节存在系统性偏差的证据，这种偏差可能是IDDM的细胞介导免疫（Th1）或Graves病的体液免疫（Th2）。
Disturbed immune regulation has been postulated to be crucial in the pathogenesis of IDDM and other autoimmune or allergic diseases. We therefore tested the hypothesis of a general bias in the peripheral immune system in patients with recent-onset IDDM or Graves' disease in comparison to healthy control subjects by studying whole blood cultures stimulated with phytohemagglutinin. Cells from IDDM patients (n = 53) produced significantly higher amounts of Th1 cytokines gamma-interferon (IFN-gamma) (P = 0.028) and tumor necrosis factor alpha (TNF-alpha) (P = 0.007) than normal control subjects (n = 56), while Th2 cytokine levels (interleukin [IL]-4, IL-10) were similar. Low levels of islet cell antibodies (ICAs) in IDDM patients were associated with high levels of Th1 and Th2 cytokines. Antibodies to GAD, ICA512, or insulin did not correlate with individual cytokine profiles. Also, HLA-DQ types did not significantly correlate with either Th1 or Th2 cytokine production. Conversely, whole blood cultures from patients with Graves' disease (n = 18) produced significantly less TNF-alpha and IL-4 than normal subjects (P = 0.001-0.006). However, when the balance between Th1 and Th2 cytokine production was analyzed in individuals, the ratio between IFN-gamma or TNF-alpha and IL-4 or IL-10 was clearly biased toward Th1 reactivity in patients with IDDM (P = 0.0001), while a dominance of Th2 cytokine production was seen in Graves' disease (P = 0.0001). The ratio of counterregulatory cytokines appeared to be the most reliable marker of the individual disease process. This study provides first evidence of a systemic bias in the immune regulation of humans, which might be either toward cell-mediated immunity (Th1) in IDDM or humoral immunity (Th2) in Graves' disease.