Jergović Mladen, Tomičević Marko, Vidović Anđelko, Bendelja Krešo, Savić Ana, Vojvoda Valerija, Rac Dijana, Lovrić-Čavar Davorka, Rabatić Sabina, Jovanovic Tanja, Sabioncello Ante
Centre for Research and Knowledge Transfer in Biotechnology, University of Zagreb, Zagreb, Croatia.
Dr. Josip Benčević General Hospital, Slavonski Brod, Croatia.
Prog Neuropsychopharmacol Biol Psychiatry. 2014 Oct 3;54:275-83. doi: 10.1016/j.pnpbp.2014.06.010. Epub 2014 Jun 28.
There is increasing evidence that chronic stress accelerates telomere erosion in leukocytes/peripheral blood mononuclear cells (PBMCs). However, functional changes associated with telomere shortening are poorly understood. We hypothesized that war veterans with PTSD would have shorter telomeres in PBMCs and that these cells might exhibit changes in measures of immune reactivity such as proliferation, cytokine production and expression of regulators of immune responses.
We measured relative telomere length and basal telomerase activity in PBMCs of 62 individuals (PTSD patients (N=30); age-matched healthy controls (N=17), elderly volunteers (N=15)). In parallel, we have assessed proliferation of activated T cells, interferon (IFN)-γ, interleukin (IL)-2, IL-4, tumor necrosis factor (TNF)-α and IL-6 cytokine production and expression of programmed death 1 (PD-1) receptor and its ligand PD-L1 on activated T cells.
Middle-aged war veterans with current PTSD had shorter PBMC telomere length than their age-matched healthy controls while the elderly had the shortest telomeres. There was no difference in telomerase activity between PTSD patients and healthy controls while telomerase activity was significantly lower in the elderly. While the elderly group exhibited robust changes in immune activity such as increased production of proinflammatory cytokines (TNF-α, IL-6) and reduced proliferation of all T cells, the PTSD group showed reduced proliferative response of CD8(+) T cells to high concentrations of mitogen and reduced spontaneous production of IL-2 and IFN-γ.
This study adds to the accumulating evidence that psychological trauma and chronic stress are associated with accelerated telomere attrition. However, changes in immune function associated with stress-related telomere shortening are not well understood. Although much less pronounced in PTSD patients than in elderly persons, reduced proliferative responses of T cells accompanied by shorter telomeres might be a sign of early immunosenescence. Together with reduced production of Th1 cytokines, observed immune changes may contribute to health risks associated with PTSD.
越来越多的证据表明，慢性应激会加速白细胞/外周血单核细胞（PBMC）中端粒的损耗。然而，与端粒缩短相关的功能变化却知之甚少。我们推测，患有创伤后应激障碍（PTSD）的退伍军人PBMC中的端粒会更短，并且这些细胞可能会在免疫反应性指标上出现变化，如增殖、细胞因子产生以及免疫反应调节因子的表达。
我们测量了62名个体（PTSD患者（n = 30）；年龄匹配的健康对照者（n = 17），老年志愿者（n = 15））PBMC中的相对端粒长度和基础端粒酶活性。同时，我们评估了活化T细胞的增殖、干扰素（IFN）-γ、白细胞介素（IL）-2、IL-4、肿瘤坏死因子（TNF）-α和IL-6的细胞因子产生，以及活化T细胞上程序性死亡1（PD-1）受体及其配体PD-L1的表达。
患有当前PTSD的中年退伍军人PBMC端粒长度比其年龄匹配的健康对照者短，而老年人的端粒最短。PTSD患者和健康对照者之间的端粒酶活性没有差异，而老年人的端粒酶活性显著更低。虽然老年组在免疫活性方面表现出明显变化，如促炎细胞因子（TNF-α、IL-6）产生增加以及所有T细胞增殖减少，但PTSD组显示CD8(+) T细胞对高浓度丝裂原的增殖反应降低，以及IL-2和IFN-γ的自发产生减少。
这项研究进一步证明了心理创伤和慢性应激与端粒损耗加速有关。然而，与应激相关的端粒缩短所伴随的免疫功能变化尚未完全明确。虽然在PTSD患者中不如在老年人中明显，但T细胞增殖反应降低并伴有端粒缩短可能是早期免疫衰老的一个迹象。连同Th1细胞因子产生减少一起，观察到的免疫变化可能会导致与PTSD相关的健康风险。
