The effects of vagus nerve stimulation on pro- and anti-inflammatory cytokines in humans: a preliminary report.
OBJECTIVE
Vagus nerve stimulation (VNS) is a novel therapy in resistant epilepsy, and is undergoing clinical trials in resistant depression. The mechanism of action of VNS is assumed to be due to modulation of deep brain structures via its afferent connections. As the vagus nerve has potentially important immunological actions that may have relevance to its therapeutic effects, we hypothesised that an additional mechanism may occur via vagally mediated actions on cytokine synthesis.


METHODS
Patients (n=10) with resistant depression were studied in the weeks prior to, and 3 months following, implantation of a vagus nerve stimulator. No medication changes were made during the course of the study. High-sensitivity ELISA kits were used to measure plasma IL-1 beta, IL-6, TNF-alpha, IL-10 and TGF-beta concentrations. C-reactive protein (CRP) was measured using a high sensitivity immunonephelometry assay.


RESULTS
There were highly significant increases in the plasma levels of IL-6, TNF-alpha and TGF-beta. Increases seen with IL-10 and IL-1 beta were not significant. Plasma CRP levels were unchanged.


CONCLUSIONS
VNS is associated with marked peripheral increases in pro- and anti-inflammatory circulating cytokines. Such changes are unlikely to be non-specific inflammatory reactions, reflected by CRP levels. In view of gathering evidence supporting a role for the immune system in modulating affect, as well as seizure activity, these effects of VNS may be therapeutically relevant.
Corcoran
Ciaran
C
Department of Psychiatry, Beaumont Hospital, and Royal College of Surgeons in Ireland, Dublin, Ireland.
Connor
Thomas J
TJ
O'Keane
Veronica
V
Garland
Malcolm R
MR
D000328:Adult; D002097:C-Reactive Protein / Q000032:analysis; D016207:Cytokines / Q000097:blood*; D003863:Depression / Q000276:immunology / Q000628:therapy*; D004599:Electric Stimulation Therapy; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D016212:Transforming Growth Factor beta / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D014630:Vagus Nerve / Q000276:immunology*
D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D002097:C-Reactive Protein