Effect of Vagal Nerve Stimulation on Systemic Inflammation and Cardiac Autonomic Function in Patients with Refractory Epilepsy

Barone, Lucy; Colicchio, Gabriella; Policicchio, Domenico; Clemente, Francesca Di; Monaco, Antonio Di; Meglio, Mario; Lanza, Gaetano Antonio; Crea, Filippo

doi:10.1159/000127360

Cited by 42 publications

(34 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Nevertheless, a small number of observational studies have been performed, yielding conflicting results. Two studies demonstrated no change in plasma cytokine levels 3 [33] or 7 [34] months after VNS, while another study found that plasma cytokine levels had actually increased after 3 months of VNS [35] . The interpretation of these studies is hampered by the fact that no inflammatory trigger was present in these patients with epilepsy or depression.…”

Section: Human Studies Into the Anti-inflammatory Effects Of The Vagumentioning

confidence: 98%

“…The interpretation of these studies is hampered by the fact that no inflammatory trigger was present in these patients with epilepsy or depression. As such, circulating cytokine levels in many cases were undetectable or very low [33][34][35] . Another study investigated the effects of VNS for 6 months and 3 weeks on cyto-kine production by ex vivo stimulation of monocytes with LPS.…”

Section: Human Studies Into the Anti-inflammatory Effects Of The Vagumentioning

confidence: 99%

See 1 more Smart Citation

Modulation of the Innate Immune Response through the Vagus Nerve

Kox

Pickkers

2015

Nephron

View full text Add to dashboard Cite

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.

show abstract

Section: Human Studies Into the Anti-inflammatory Effects Of The Vagumentioning

confidence: 98%

Section: Human Studies Into the Anti-inflammatory Effects Of The Vagumentioning

confidence: 99%

Modulation of the Innate Immune Response through the Vagus Nerve

Kox

Pickkers

2015

Nephron

View full text Add to dashboard Cite

show abstract

“…In these clinical settings, several groups have failed to detect a clear effect of vagal stimulation on serum levels of inflammatory cytokines. [118][119][120] However, in epileptic patients, intraoperative or chronic electrical vagal nerve stimulation were able to significantly inhibit TNF-α release in whole blood samples treated with lipopolysaccharide in vitro. 121 One possible explanation could be that side effects due to activation of the recurrent laryngeal nerve may hamper adequate nerve stimulation to achieve the anti-inflammatory effect of VN stimulation.…”

Section: Human Evidencementioning

confidence: 99%

The vagal innervation of the gut and immune homeostasis

Matteoli

Gomez‐Pinilla

Giovangiulio

et al. 2015

Autonomic Neuroscience

View full text Add to dashboard Cite

The central nervous system interacts dynamically with the immune system to modulate inflammation through humoral and neural pathways. Recently, in animal models of sepsis, the vagus nerve (VN) has been proposed to play a crucial role in the regulation of the immune response, also referred to as the cholinergic anti-inflammatory pathway. The VN, through release of acetylcholine, dampens immune cell activation by interacting with α-7 nicotinic acetylcholine receptors. Recent evidence suggests that the vagal innervation of the gastrointestinal tract also plays a major role controlling intestinal immune activation. Indeed, VN electrical stimulation potently reduces intestinal inflammation restoring intestinal homeostasis, whereas vagotomy has the reverse effect. In this review, we will discuss the current understanding concerning the mechanisms and effects involved in the cholinergic anti-inflammatory pathway in the gastrointestinal tract. Deeper investigation on this counter-regulatory neuroimmune mechanism will provide new insights in the cross-talk between the nervous and immune system leading to the identification of new therapeutic targets to treat intestinal immune disease.

show abstract

“…VNS has been reported to increase circulating pro-and anti-inflammatory cytokines in depressed patients [17], but in epilepsy patients the results are inconclusive: VNS has been shown to alter the immune response [18] but fails to affect systemic inflammation [19,20]. So far there are no studies available evaluating neuro-immunomodulation by VNS in children.…”

Section: Introductionmentioning

confidence: 99%

The Effects of Vagus Nerve Stimulation on Pro- and Anti-Inflammatory Cytokines in Children with Refractory Epilepsy: An Exploratory Study

Aalbers

Klinkenberg

Rijkers

et al. 2012

Neuroimmunomodulation

View full text Add to dashboard Cite

Objectives: The vagus nerve has important immunological and anti-inflammatory actions that might be relevant to the beneficial effects of vagus nerve stimulation (VNS). Therefore, we conducted an exploratory study on VNS effects on cytokine levels in plasma and cerebrospinal fluid of children suffering from refractory epilepsy. Moreover, as predictors of the response are lacking, we also aimed to determine if cytokine changes predict the clinical response. Methods: VNS was performed according to a randomized double-blind design: plasma levels were compared between patients who received 20 weeks of high output (therapeutic) (n = 21) or low output (active control) stimulation (n = 20). Thereupon, all patients received high output stimulation for another 19 weeks; levels during this period were compared to baseline. Interictal interleukin-1β, interleukin-6, and interleukin-10 were determined by ELISA. Results: No significant changes were found between high and low output groups and between the last 19 weeks of stimulation and baseline. Changes in interleukin-1β correlated with improved IQ (τ = 0.42, p < 0.01). Lower baseline plasma levels of interleukin-6 were associated with more seizure frequency reduction [R² = 0.105 (1, 35), p = 0.050]. Conclusion: Interictal cytokine levels were not altered by VNS but baseline interleukin-6 predicted the clinical response. In the future, patient selection may be aided by determination of the cytokine profile of the patient.

show abstract

Effect of Vagal Nerve Stimulation on Systemic Inflammation and Cardiac Autonomic Function in Patients with Refractory Epilepsy

Cited by 42 publications

References 66 publications

Modulation of the Innate Immune Response through the Vagus Nerve

Modulation of the Innate Immune Response through the Vagus Nerve

The vagal innervation of the gut and immune homeostasis

The Effects of Vagus Nerve Stimulation on Pro- and Anti-Inflammatory Cytokines in Children with Refractory Epilepsy: An Exploratory Study

Contact Info

Product

Resources

About