title: 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.
abstract: BACKGROUND
  Stimulation of the vagus nerve in the so-called cholinergic antiinflammatory pathway (CAP) attenuates systemic inflammation, improving survival in animal sepsis models via α7 nicotinic acetylcholine receptors on immunocompetent cells. Because the relevance of this regulatory pathway is unknown in human sepsis, this pilot study assessed whether the α7 gene expression level in septic patients' peripheral blood mononuclear cells (PBMC) might be used to assess CAP activity and clinical outcome.
  
  
  METHODS
  The PBMCs α7 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 α7 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' α7 levels were significantly increased and returned to control values after recovery. These α7 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 α7 gene expression level is a clinically relevant marker for CAP activity in sepsis: the higher the α7 expression, the better the inflammation control and the prognosis.
authors.affiliation: Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma.
authors.forename: José L
authors.initials: JL
authors.lastname: Cedillo
authors.affiliation: Servicio de Medicina Interna.
authors.forename: Francisco
authors.initials: F
authors.lastname: Arnalich
authors.affiliation: Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma.
authors.forename: Carolina
authors.initials: C
authors.lastname: Martín-Sánchez
authors.affiliation: Servicio de Medicina Interna.
authors.forename: Angustias
authors.initials: A
authors.lastname: Quesada
authors.affiliation: Servicio de Medicina Interna.
authors.forename: Juan José
authors.initials: JJ
authors.lastname: Rios
authors.affiliation: Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma.
authors.forename: María C
authors.initials: MC
authors.lastname: Maldifassi
authors.affiliation: Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma.
authors.forename: Gema
authors.initials: G
authors.lastname: Atienza
authors.affiliation: Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas-Universidad Autónoma, Instituto de Investigacion Sanitaria IdiPAZ, Madrid, Spain.
authors.forename: Jaime
authors.initials: J
authors.lastname: Renart
authors.affiliation: Servicio de Medicina Interna.
authors.forename: Carmen
authors.initials: C
authors.lastname: Fernández-Capitán
authors.affiliation: Servicio de Neumología.
authors.forename: Francisco
authors.initials: F
authors.lastname: García-Rio
authors.affiliation: Laboratory of Tumor Immunology, Unidad de Investigación, Hospital Universitario La Paz.
authors.forename: Eduardo
authors.initials: E
authors.lastname: López-Collazo
authors.affiliation: Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma.
authors.forename: Carmen
authors.initials: C
authors.lastname: Montiel
mesh_terms: D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D002460:Cell Line; D018678:Cholinergic Agents / Q000627:therapeutic use; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000235:genetics / Q000382:microbiology; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D012333:RNA, Messenger / Q000096:biosynthesis / Q000097:blood* / Q000235:genetics; D018805:Sepsis / Q000097:blood / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D014630:Vagus Nerve / Q000502:physiology; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000235:genetics* / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D018678:Cholinergic Agents; D012333:RNA, Messenger; D064569:alpha7 Nicotinic Acetylcholine Receptor
keywords: cholinergic antiinflammatory pathway; heart rate variability; sepsis; septic patients; vagus nerve; α7 nicotinic receptors