Hanifi-Moghaddam P, Kappler S, Seissler J, Müller-Scholze S, Martin S, Roep B O, Strassburger K, Kolb H, Schloot N C
German Diabetes Clinic, German Diabetes Center, Leibniz Institute at the Heinrich-Heine-University, Düsseldorf, Germany.
Diabet Med. 2006 Feb;23(2):156-63. doi: 10.1111/j.1464-5491.2005.01743.x.
The hypothesis was tested in an exploratory study that individuals at high risk of developing Type 1 diabetes mellitus have altered systemic levels of cytokines and chemokines.
Forty-two non-diabetic first-degree relatives of patients with Type 1 diabetes mellitus were recruited. Of these, 18 had multiple islet autoantibodies (islet cell antibody, glutamic acid decarboxylase antibody, IA-2 antibody). Follow-up for 9-11 years confirmed high vs. moderate diabetes risk in islet autoantibody-positive vs. -negative relatives. Cytokines and chemokines were determined by enzyme-linked immunosorbent assay (ELISA).
Serum concentrations of classic Th1-associated cytokines (IFN-gamma, IL-12, IL-18) or Th2/Treg-associated cytokines (IL-5, IL-10, IL-13) did not significantly differ in high vs. moderate diabetes risk group. However, of six chemokines analysed, levels of CCL3 and CCL4 were increased (P = 0.0442 and P = 0.0334) while CCL2 was decreased (P = 0.0318) in the multiple islet autoantibody-positive group. No significant differences were seen for CCL5, CCL11, CXCL10. There was a significant correlation between the two closely related chemokines CCL3 and CCL4 in individuals at risk (r = 0.84, P = 0.00005), but not in the autoantibody-negative group.
Relatives at high risk of developing Type 1 diabetes mellitus have abnormal cellular immune regulation at the level of systemic chemokines. The up-regulation of CCL3 and CCL4 vs. down-regulation of CCL2 suggests opposed functions of these chemokines in the disease process. These findings need to be confirmed by independent studies.
在一项探索性研究中检验了如下假设，即1型糖尿病发病高危个体的细胞因子和趋化因子的全身水平发生了改变。
招募了42名1型糖尿病患者的非糖尿病一级亲属。其中，18人有多种胰岛自身抗体（胰岛细胞抗体、谷氨酸脱羧酶抗体、IA-2抗体）。9至11年的随访证实，胰岛自身抗体阳性与阴性亲属分别具有高与中度糖尿病风险。通过酶联免疫吸附测定（ELISA）法测定细胞因子和趋化因子。
经典Th1相关细胞因子（干扰素-γ、白细胞介素-12、白细胞介素-18）或Th2/Treg相关细胞因子（白细胞介素-5、白细胞介素-10、白细胞介素-13）的血清浓度在高糖尿病风险组与中度糖尿病风险组之间无显著差异。然而，在分析的六种趋化因子中，多种胰岛自身抗体阳性组的CCL3和CCL4水平升高（P = 0.0442和P = 0.0334），而CCL2水平降低（P = 0.0318）。CCL5、CCL11、CXCL10未见显著差异。在有风险个体中，两种密切相关的趋化因子CCL3和CCL4之间存在显著相关性（r = 0.84，P = 0.00005），但在自身抗体阴性组中无此相关性。
1型糖尿病发病高危亲属在全身趋化因子水平存在异常的细胞免疫调节。CCL3和CCL4的上调与CCL2的下调表明这些趋化因子在疾病过程中具有相反的功能。这些发现需要通过独立研究加以证实。
