Increased pro-inflammatory cytokines and an overactive hypothalamic-pituitary-adrenal (HPA) axis have both been implicated in the pathogenesis of depression. However, these explanations appear contradictory because glucocorticoids are well recognised for their anti-inflammatory effects. Two hypotheses exist to resolve this paradox: the mediating presence of glucocorticoid receptor resistance, or the possibility that glucocorticoids can potentiate inflammatory processes in some circumstances. We sought to investigate these hypotheses in a cell model with significant relevance to depression: human hippocampal progenitor cells. We demonstrated that dexamethasone in vitro given for 24 hours and followed by a 24-hour rest interval before an immune challenge potentiates inflammatory effects in these neural cells, that is, increases the IL-6 protein secretion induced by stimulation with IL-1β (10ng/mL for 24 hours) by +49% (P<0.05) at a concentration of 100nM and by +70% (P<0.01) for 1μM. These effects are time- and dose-dependent and require activation of the glucocorticoid receptor. Gene expression microarray assays using Human Gene 2.1st Array Strips demonstrated that glucocorticoid treatment up-regulated several innate immune genes, including chemokines and Nod-like receptor, NLRP6; using transcription factor binding motifs we found limited evidence that glucocorticoid resistance was induced in the cells. Our data suggests a mechanism by which stress may prime the immune system for increased inflammation and suggests that stress and inflammation may be synergistic in the pathogenesis of depression.

中文翻译：

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糖皮质激素通过上调炎症通路引发人海马细胞的炎症反应

增加的促炎细胞因子和过度活跃的下丘脑-垂体-肾上腺（HPA）轴都与抑郁症的发病机制有关。然而，这些解释似乎是矛盾的，因为糖皮质激素的抗炎作用已得到广泛认可。有两个假设可以解决这个悖论：糖皮质激素受体抗性的介导存在，或者糖皮质激素在某些情况下可以增强炎症过程的可能性。我们试图在与抑郁症显着相关的细胞模型中研究这些假设：人类海马祖细胞。我们证明，在免疫挑战之前，在体外给予地塞米松 24 小时，然后休息 24 小时会增强这些神经细胞的炎症作用，也就是说，在 100nM 浓度和 1μM 浓度下，IL-1β（10ng/mL，24 小时）刺激诱导的 IL-6 蛋白分泌增加 +49%（P<0.05）和 +70%（P<0.01）。这些作用是时间和剂量依赖性的，需要激活糖皮质激素受体。使用 Human Gene 2.1st Array Strips 的基因表达微阵列分析表明，糖皮质激素治疗上调了几种先天免疫基因，包括趋化因子和 Nod 样受体 NLRP6；使用转录因子结合基序，我们发现有限的证据表明在细胞中诱导了糖皮质激素抗性。我们的数据表明压力可能会引发免疫系统增加炎症的机制，并表明压力和炎症可能在抑郁症的发病机制中具有协同作用。