Vagus Nerve Stimulation in Refractory Epilepsy: Effects on Pro- and Anti-Inflammatory Cytokines in Peripheral Blood

Objective: The vagus nerve has important immunological functions
that may be relevant for its anticonvulsive action. We postulate
that this anticonvulsive action is activated by a shift in the
immune system resulting in a reduction of neurotoxic and an
increase of neuroprotective tryptophan metabolites. Methods: Eleven
patients with refractory epilepsy and 11 controls matched for age
and gender were included in this study. The primary outcome measure
was a 50% seizure reduction. Other variables were pro-inflammatory
cytokines IL-6 and TNF-alpha, anti-inflammatory cytokine IL-10,
cortisol, and the tryptophan metabolites 3-hydroxykynurenine
(3-OH-KYN), kynurenic acid (KYNA), kynurenine, serotonin (5-HT) and
5-hydroxyindol acetic acid (5-HIAA). Blood samples were scheduled
during baseline, and in week 28 of add-on treatment. Results: IL-6
levels were higher in the responders than in the control group, and
decreased after vagus nerve stimulation (VNS), whereas IL-10 was
low and increased after VNS. In nonresponders, VNS resulted in an
increase of IL-6 plasma levels and in a decrease of IL-10. Cortisol
concentrations are higher in the epilepsy group than in the control
group. After VNS, these concentrations decreased. The
concentrations of the tryptophan metabolites were lower in the
epilepsy group than in the control group. The KYNA ratios are
defined as the ratio of neuroprotective KYNA versus neurotoxic
3-OH-KYN and KYNA versus neurotoxic kynurenine: these ratios were
lower in epilepsy patients than in controls, and they both
moderately increased after VNS. Conclusion: The outcome of this
preliminary study indicates that VNS causes a rebalancing of the
immune system. This results in: (1) a reduction of neurotoxic and
an increase of neuroprotective kynurenine metabolites and (2) in
the normalization of cortisol levels. Copyright (C) 2010 S. Karger
AG, Basel