Usefulness of α7 Nicotinic Receptor Messenger RNA Levels in Peripheral Blood Mononuclear Cells as a Marker for Cholinergic Antiinflammatory Pathway Activity in Septic Patients: Results of a Pilot Study
Usefulness of α7 Nicotinic Receptor Messenger RNA Levels in Peripheral Blood Mononuclear Cells as a Marker for Cholinergic Antiinflammatory Pathway Activity in Septic Patients: Results of a Pilot Study
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DOI：
10.1093/infdis/jiu425
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发表时间：
2015-01-01
影响因子：
6.4
通讯作者：
Montiel, Carmen
中科院分区：
文献类型：
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作者：
Cedillo, Jose L.;Arnalich, Francisco;Montiel, Carmen
背景在所谓的胆碱能抗炎途径（CAP）中刺激迷走神经可以减轻全身炎症，通过免疫活性细胞上的α 7尼古丁乙酰胆碱受体提高动物败血症模型的生存率。由于这种调节途径在人类脓毒症中的相关性是未知的，因此该初步研究评估了脓毒症患者外周血单核细胞（PBMC）中的α 7基因表达水平是否可用于评估CAP活性和临床结果。通过实时定量逆转录聚合酶链反应测定33例对照和33例患者入组时和出院后的PBMC α 7信使RNA水平。分析数据以发现α 7水平、作为CAP活性间接反映的迷走神经介导的心率变异性、不同炎症标志物的血清浓度和临床病程之间的显著相关性。脓毒症患者的α 7水平显著升高，并在恢复后恢复至对照值。这些α 7水平与迷走神经心脏输入直接相关，与患者炎症状态的程度、疾病严重程度和临床结局呈负相关。本研究揭示PBMC α 7基因表达水平是脓毒症CAP活性的临床相关标志物：α 7表达越高，炎症控制和预后越好。
Background. Stimulation of the vagus nerve in the so-called cholinergic antiinflammatory pathway (CAP) attenuates systemic inflammation, improving survival in animal sepsis models via alpha 7 nicotinic acetylcholine receptors on immunocompetent cells. Because the relevance of this regulatory pathway is unknown in human sepsis, this pilot study assessed whether the alpha 7 gene expression level in septic patients' peripheral blood mononuclear cells (PBMC) might be used to assess CAP activity and clinical outcome.Methods. The PBMCs alpha 7 messenger RNA levels were determined by real-time quantitative reverse-transcription polymerase chain reaction in 33 controls and 33 patients at enrollment and after their hospital discharge. Data were analyzed to find significant associations between alpha 7 level, vagally mediated heart rate variability as an indirect reflection of CAP activity, serum concentrations of different inflammation markers, and clinical course.Results. Septic patients' alpha 7 levels were significantly increased and returned to control values after recovery. These alpha 7 levels correlated directly with the vagal heart input and inversely with the magnitude of the patient's inflammatory state, disease severity, and clinical outcome.Conclusions. This study reveals that the PBMC alpha 7 gene expression level is a clinically relevant marker for CAP activity in sepsis: the higher the alpha 7 expression, the better the inflammation control and the prognosis.