Journal of Clinical Immunology

, Volume 30, Issue 2, pp 213–220 | Cite as

The Vagus Nerve and Nicotinic Receptors Involve Inhibition of HMGB1 Release and Early Pro-inflammatory Cytokines Function in Collagen-Induced Arthritis

  • Tong Li
  • Xiaoxia Zuo
  • Yaou Zhou
  • Yanping Wang
  • Hanping Zhuang
  • Lingli Zhang
  • Huali Zhang
  • Xianzhong Xiao
Article
First Online:
Received:
Accepted:

Abstract

Objectives

The cholinergic anti-inflammatory pathway, a vagus nerve-dependent mechanism, inhibits cytokine releases in models of acute inflammatory disease. We investigated the efficacy and elucidated the possible mechanism of the cholinergic anti-inflammatory pathway on collagen-induced arthritis (CIA) in mice.

Methods

Fifty-six male DBA/1 mice were divided into four groups: control mice (sham vagotomy + phosphate-buffered saline; shamVGX+PBS), model mice (shamVGX+PBS+CIA), vagotomy mice (VGX+PBS+CIA), and nicotine (Nic) mice (shamVGX+Nic+CIA). We subjected mice to left-side cervical vagotomy 4 days before induction of arthritis. Mice in the nicotine group were injected with nicotine (250 μg/kg per day) 4 days before arthritis induction. Arthritis score was measured and histopathologic assessment of joint sections carried out. The concentration of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10 in serum were evaluated by ELISA. Expression of high-mobility group box chromosomal protein 1(HMGB1) was evaluated by immunohistochemical staining of joints.

Results

Vagotomy exaggerated, whereas nicotine attenuated, clinical arthritis. Histopathologic findings confirmed that nicotine reduced infiltration of inflammatory cell and bone destruction. Expression of TNF-α and IL-6 decreased in nicotine-pretreated mice compared with model and vagotomy mice; IL-10 levels were not significantly different between the model group and nicotine group. Nicotine reduced the expression and translocation of HMGB1 in the inflamed joints of CIA mice.

Conclusions

The cholinergic anti-inflammatory pathway has an anti-inflammatory role in the pathophysiology of rheumatoid arthritis (RA) via inhibiting HMGB1 release and early pro-inflammatory cytokines function. Study of this pathway could be used for RA therapy.

Keywords

Rheumatoid arthritis cholinergic pathway inflammation 

Abbreviations

CIA

Collagen-induced arthritis

ShamVGX

Sham vagotomy

PBS

Phosphate-buffered saline

Nic

Nicotine

TNF

Tumor necrosis factor

IL

Interleukin

HMGB

High-mobility group box chromosomal protein

RA

Rheumatoid arthritis

TGF

Transforming growth factor

CNS

Central nervous system

MIP

Macrophage inflammatory protein

LPS

Lipopolysaccharide

ELISA

Enzyme-linked immunosorbent assay

EDTA

Ethylene diamine tetra-acetic acid

H&E

Hematoxylin and erosin

PGE

Prostaglandin E

MMPs

Metallproteinases

NO

Nitric oxide

TNFR

TNF receptor

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Notes

Acknowledgements

This work was supported by grant from the National Natural Science Foundation of China [30671947].

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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Tong Li
    • 1
  • Xiaoxia Zuo
    • 1
  • Yaou Zhou
    • 1
  • Yanping Wang
    • 1
  • Hanping Zhuang
    • 2
  • Lingli Zhang
    • 3
  • Huali Zhang
    • 3
  • Xianzhong Xiao
    • 3
  1. 1.Department of Rheumatology, Xiangya HospitalCentral South UniversityChangshaPeople’s Republic of China
  2. 2.Department of Geratology, Xiangya HospitalCentral South UniversityChangshaPeople’s Republic of China
  3. 3.Laboratory of Shock, Department of Pathophysiology, Xiangya School of MedicineCentral South UniversityChangshaPeople’s Republic of China

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