Wirtz Petra H, von Känel Roland, Schnorpfeil Pia, Ehlert Ulrike, Frey Karl, Fischer Joachim E
Department of Behavioral Sciences, Swiss Federal Institute of Technology, Zurich, Switzerland.
Psychosom Med. 2003 Jul-Aug;65(4):672-8. doi: 10.1097/01.psy.0000062529.39901.c7.
Proinflammatory changes are thought to link vital exhaustion with adverse cardiovascular outcomes. Monocytes play a central role in the pathogenesis of atherosclerotic lesions and are a major source of circulating cytokines. We hypothesized that vital exhaustion may alter the regulation of monocyte activity, as measured by lipopolysaccharide (LPS)-stimulated and glucocorticoid inhibited release of the proinflammatory cytokine interleukin-6 (IL-6).
In 166 middle-aged apparently healthy men, vital exhaustion was measured by the Shortened Maastricht Exhaustion Questionnaire. Subjects in the highest quartile (highly exhausted, N= 38) were compared with those in the second and third quartiles (moderately exhausted N= 89) vs. those in the lowest quartile (nonexhausted, N= 39) in terms of plasma C-reactive protein (CRP) and tumor necrosis factor-alpha (TNF-alpha) levels, and as to IL-6 release after LPS stimulation in vitro. Inhibition of IL-6 release was determined by coincubation with increasing concentrations of dexamethasone. Monocyte glucocorticoid sensitivity was defined as the dexamethasone concentration inhibiting IL-6 release by 50%.
Highly exhausted individuals had higher CRP levels than nonexhausted subjects (p=.008). LPS-stimulated IL-6 release was not significantly different between groups. However, in highly exhausted participants, dexamethasone was less able to inhibit IL-6 release (p=.010), and the glucocorticoid sensitivity was lower (p=.003) than in nonexhausted subjects.
In highly exhausted individuals, glucocorticoids exert less suppressive action on monocyte IL-6 release than in nonexhausted subjects. This finding points to altered regulation of monocyte cytokine production as one possible pathway linking exhaustion with atherosclerosis.
促炎变化被认为是将活力耗竭与不良心血管结局联系起来的纽带。单核细胞在动脉粥样硬化病变的发病机制中起核心作用，并且是循环细胞因子的主要来源。我们推测，活力耗竭可能会改变单核细胞活性的调节，这可以通过脂多糖（LPS）刺激和糖皮质激素抑制促炎细胞因子白细胞介素-6（IL-6）的释放来衡量。
在166名表面健康的中年男性中，通过简化的马斯特里赫特倦怠问卷来测量活力耗竭情况。将最高四分位数组（高度倦怠，N = 38）的受试者与第二和第三四分位数组（中度倦怠，N = 89）的受试者以及最低四分位数组（无倦怠，N = 39）的受试者在血浆C反应蛋白（CRP）和肿瘤坏死因子-α（TNF-α）水平方面进行比较，并比较体外LPS刺激后IL-6的释放情况。通过与浓度递增的地塞米松共同孵育来确定IL-6释放的抑制情况。单核细胞糖皮质激素敏感性定义为抑制IL-6释放50%时的地塞米松浓度。
高度倦怠的个体比无倦怠的受试者CRP水平更高（p = 0.008）。各组之间LPS刺激的IL-6释放没有显著差异。然而，在高度倦怠的参与者中，地塞米松抑制IL-6释放的能力较弱（p = 0.010），且糖皮质激素敏感性低于无倦怠的受试者（p = 0.003）。
与无倦怠的受试者相比，在高度倦怠的个体中，糖皮质激素对单核细胞IL-6释放的抑制作用较小。这一发现表明单核细胞细胞因子产生的调节改变是将倦怠与动脉粥样硬化联系起来的一种可能途径。
