Institute of Medical Psychology and Behavioral Immunobiology, University of Duisburg-Essen, Essen, Germany.
PLoS One. 2011;6(12):e28330. doi: 10.1371/journal.pone.0028330. Epub 2011 Dec 2.
Clinical and experimental evidence document that inflammation and increased peripheral cytokine levels are associated with depression-like symptoms and neuropsychological disturbances in humans. However, it remains unclear whether and to what extent cognitive functions like memory and attention are affected by and related to the dose of the inflammatory stimulus. Thus, in a cross-over, double-blind, experimental approach, healthy male volunteers were administered with either placebo or bacterial lipopolysaccharide (LPS) at doses of 0.4 (n = 18) or 0.8 ng/kg of body weight (n = 16). Pro- and anti-inflammatory cytokines, norephinephrine and cortisol concentrations were analyzed before and 1, 1.75, 3, 4, 6, and 24 h after injection. In addition, changes in mood and anxiety levels were determined together with working memory (n-back task) and long term memory performance (recall of emotional and neutral pictures of the International Affective Picture System). Endotoxin administration caused a profound transient physiological response with dose-related elevations in body temperature and heart rate, increases in plasma interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-α and IL-1 receptor antagonist (IL-1ra), salivary and plasma cortisol, and plasma norepinephrine. These changes were accompanied by dose-related decreased mood and increased anxiety levels. LPS administration did not affect accuracy in working memory performance but improved reaction time in the high-dose LPS condition compared to the control conditon. In contrast, long-term memory performance was impaired selectively for emotional stimuli after administration of the lower but not of the higher dose of LPS. These data suggest the existence of at least two counter-acting mechanisms, one promoting and one inhibiting cognitive performance during acute systemic inflammation.
临床和实验证据表明，炎症和外周细胞因子水平升高与人类的抑郁症状和神经心理障碍有关。然而，目前尚不清楚认知功能（如记忆和注意力）是否以及在何种程度上受到炎症刺激剂量的影响，以及与认知功能相关。因此，采用交叉、双盲、实验的方法，给 18 名健康男性志愿者分别注射 0.4ng/kg（n=18）或 0.8ng/kg（n=16）的安慰剂或细菌脂多糖（LPS）。在注射前以及注射后 1、1.75、3、4、6 和 24 小时，分析促炎和抗炎细胞因子、去甲肾上腺素和皮质醇浓度。此外，还测定了情绪和焦虑水平的变化，以及工作记忆（n-back 任务）和长时记忆表现（对国际情感图片系统的情绪和中性图片的回忆）。内毒素给药引起了明显的短暂生理反应，体温和心率呈剂量相关性升高，血浆白细胞介素（IL）-6、IL-10、肿瘤坏死因子（TNF）-α和 IL-1 受体拮抗剂（IL-1ra）、唾液和血浆皮质醇以及血浆去甲肾上腺素增加。这些变化伴随着与剂量相关的情绪下降和焦虑增加。LPS 给药不影响工作记忆表现的准确性，但与对照条件相比，高剂量 LPS 条件下反应时间改善。相比之下，较低剂量 LPS 给药不会选择性地影响长期记忆表现，而较高剂量 LPS 给药会选择性地影响长期记忆表现。这些数据表明，在急性全身炎症期间，至少存在两种相互拮抗的机制，一种促进，一种抑制认知表现。
