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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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.

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