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Peer-reviewedCC BY 4.0The Journal of Physiological Sciences : JPS

Circulatory context determines the anti-inflammatory efficacy of post-sepsis vagus nerve stimulation

  • Norito Washimine1,2
  • Kaori Yagishita1
  • Sayumi Matsuo1,2
  • Kanoko Washimine1,2
  • Chia-Hsien Wu1
  • Yasuna Nakamura1
  • Ryusuke Umene1,2
  • Tomoya Nishino2
  • Tsuyoshi Inoue1
  1. 1Department of Physiology of Visceral Function and Body Fluid, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan
  2. 2Department of Nephrology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan
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Abstract

Activation of the cholinergic anti-inflammatory pathway (CAP), including vagus nerve stimulation (VNS), suppresses inflammatory cytokine production and has shown efficacy in experimental sepsis when applied prior to sepsis induction. However, VNS before sepsis onset is rarely feasible in clinical practice, and whether VNS remains effective after sepsis onset is unclear. Using a lipopolysaccharide-induced mouse sepsis model, we evaluated VNS applied before and after sepsis onset. VNS applied before sepsis onset significantly reduced plasma TNF-α levels, whereas VNS applied after sepsis onset failed to suppress inflammation. Although post-sepsis VNS did not worsen hypotension or organ dysfunction, it was associated with increased lactate accumulation. Notably, fluid resuscitation restored the anti-inflammatory effect of VNS and reduced lactate levels. These findings suggest that CAP responsiveness depends on the host’s physiological state. Impaired circulation and metabolic stress may limit CAP activation during sepsis, while circulatory stabilization appears necessary for effective inflammatory control.

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Cite

BibTeXRIS
BibTeX
@article{washimine2026circulatory,
  title = {{Circulatory context determines the anti-inflammatory efficacy of post-sepsis vagus nerve stimulation}},
  author = {Norito Washimine and Kaori Yagishita and Sayumi Matsuo and Kanoko Washimine and Chia-Hsien Wu and Yasuna Nakamura and Ryusuke Umene and Tomoya Nishino and Tsuyoshi Inoue},
  journal = {The Journal of Physiological Sciences : JPS},
  year = {2026},
  month = oct,
  doi = {10.1016/j.jphyss.2026.100111},
  url = {https://doi.org/10.1016/j.jphyss.2026.100111},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Circulatory context determines the anti-inflammatory efficacy of post-sepsis vagus nerve stimulation
AU  - Norito Washimine
AU  - Kaori Yagishita
AU  - Sayumi Matsuo
AU  - Kanoko Washimine
AU  - Chia-Hsien Wu
AU  - Yasuna Nakamura
AU  - Ryusuke Umene
AU  - Tomoya Nishino
AU  - Tsuyoshi Inoue
PY  - 2026
DA  - 2026/10/15
JO  - The Journal of Physiological Sciences : JPS
DO  - 10.1016/j.jphyss.2026.100111
UR  - https://doi.org/10.1016/j.jphyss.2026.100111
AB  - Activation of the cholinergic anti-inflammatory pathway (CAP), including vagus nerve stimulation (VNS), suppresses inflammatory cytokine production and has shown efficacy in experimental sepsis when applied prior to sepsis induction. However, VNS before sepsis onset is rarely feasible in clinical practice, and whether VNS remains effective after sepsis onset is unclear. Using a lipopolysaccharide-induced mouse sepsis model, we evaluated VNS applied before and after sepsis onset. VNS applied before sepsis onset significantly reduced plasma TNF-α levels, whereas VNS applied after sepsis onset failed to suppress inflammation. Although post-sepsis VNS did not worsen hypotension or organ dysfunction, it was associated with increased lactate accumulation. Notably, fluid resuscitation restored the anti-inflammatory effect of VNS and reduced lactate levels. These findings suggest that CAP responsiveness depends on the host’s physiological state. Impaired circulation and metabolic stress may limit CAP activation during sepsis, while circulatory stabilization appears necessary for effective inflammatory control.
SN  - 1880-6546
SN  - 1880-6562
ER  -