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

Cedillo, José Luis; Arnalich, Francisco; Martín-Sánchez, Carolina; Quesada, A. González; Ríos, Juan José; Maldifassi, María Constanza; Atienza, G.; Renart, Jaime; Fernández‐Capitán, Carmen; García‐Río, Francisco; López-Collazo, Eduardo; Montiel, Carmen

doi:10.1093/infdis/jiu425

Cited by 43 publications

(47 citation statements)

References 38 publications

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“…Therefore, the pharmacological α7nAchR activation of the cholinergic anti-inflammatory pathway characterizes an alternative approach to treating sepsis [66] and its importance has been supported by clinical studies. One of these studies describes that the α7 nAchR gene expression levels in peripheral blood mononuclear cells of septic patients could be considered a clinical marker for sepsis prognostic, because higher α7nAchR expression is associated with a more efficient control of inflammation and subsequently lower disease severity [67]. …”

Section: The Inflammatory Reflexmentioning

confidence: 99%

Therapeutic potential and limitations of cholinergic anti-inflammatory pathway in sepsis

Kanashiro

Sônego

Ferreira

et al. 2017

Pharmacological Research

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Sepsis is one of the main causes of mortality in hospitalized patients. Despite the recent technical advances and the development of novel generation of antibiotics, severe sepsis remains a major clinical and scientific challenge in modern medicine. Unsuccessful efforts have been dedicated to the search of therapeutic options to treat the deleterious inflammatory components of sepsis. Recent findings on neuronal networks controlling immunity raised expectations for novel therapeutic strategies to promote the regulation of sterile inflammation, such as autoimmune diseases. Interesting studies have dissected the anatomical constituents of the so-called “cholinergic anti-inflammatory pathway”, suggesting that electrical vagus nerve stimulation and pharmacological activation of beta-2 adrenergic and alpha-7 nicotinic receptors could be alternative strategies for improving inflammatory conditions. However, the literature on infectious diseases, such as sepsis, is still controversial and, therefore, the real therapeutic potential of this neuroimmune pathway is not well defined. In this review, we will discuss the beneficial and detrimental effects of neural manipulation in sepsis, which depend on the multiple variables of the immune system and the nature of the infection. These observations suggest future critical studies to validate the clinical implications of vagal parasympathetic signaling in sepsis treatment.

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Section: The Inflammatory Reflexmentioning

confidence: 99%

Therapeutic potential and limitations of cholinergic anti-inflammatory pathway in sepsis

Kanashiro

Sônego

Ferreira

et al. 2017

Pharmacological Research

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“…Nevertheless, as a very recent study showed that α7nAChR mRNA levels in peripheral blood mononuclear cells of septic patients were increased as well as directly related with vagal HRV parameters and inversely with the extent of inflammation, severity of disease and clinical outcome [60] , this might serve as an alternative end point to determine vagus nerve activity.…”

Section: Future Perspectivesmentioning

confidence: 99%

Modulation of the Innate Immune Response through the Vagus Nerve

Kox

Pickkers

2015

Nephron

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The innate immune system is a defense mechanism that is of vital importance to our survival. However, excessive or unwanted activation of the innate immune system, which can occur in major surgery, sepsis, trauma, ischemia-reperfusion injury and autoimmune diseases, can lead to damage of the kidneys and other organs. Therefore, therapeutic approaches aimed at attenuating the innate immune response could have beneficial effects in these conditions. The vagus nerve exerts anti-inflammatory effects through the so-called cholinergic anti-inflammatory pathway. Since its discovery, numerous animal studies have shown beneficial effects of stimulation of this pathway in models of inflammatory diseases, either through (electrical) stimulation of the vagus nerve or pharmacological approaches. However, human data are very scarce. In this review, we present an overview of the molecular and anatomical bases of the cholinergic anti-inflammatory pathway, but mainly focus on human studies. We discuss the difficulties and drawbacks associated with investigating this pathway in humans, and finally, we provide future perspectives.

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“…Perhaps, it is possible that the trial examples included are healthy volunteers with LPS administration, which can not imitate complicated severe sepsis in patients and therefore is difficult to get positive results. On the other hand, Cedillo et al (51) carried out a pilot study to search the regulatory pathway in human sepsis, and found that α7 gene expression levels were closely associated with inflammation control and the prognosis, indicating that CAP does exist in sepsis patients and its effluent pathway receptor may be a useful biomarker for assessing prognosis for sepsis patients.…”

Section: Prospectsmentioning

confidence: 99%

Vagal Nerve Stimulation: A Potentially Useful Adjuvant to Treatment of Sepsis

Yang¹,

Xue²,

Sun³

et al. 2018

J Anesth Perioper Med

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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: 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.

Cited by 43 publications

References 38 publications

Therapeutic potential and limitations of cholinergic anti-inflammatory pathway in sepsis

Therapeutic potential and limitations of cholinergic anti-inflammatory pathway in sepsis

Modulation of the Innate Immune Response through the Vagus Nerve

Vagal Nerve Stimulation: A Potentially Useful Adjuvant to Treatment of Sepsis

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