The vagus nerve and nicotinic receptors involve inhibition of HMGB1 release and early pro-inflammatory cytokines function in collagen-induced arthritis.

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 microg/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)-alpha, 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-alpha 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.

• Authors: Tong Li, Xiaoxia Zuo, Yaou Zhou, Yanping Wang, Hanping Zhuang, Lingli Zhang, Huali Zhang, Xianzhong Xiao
• Journal: Journal of clinical immunology (J Clin Immunol) Vol. 30 Issue 2 Pg. 213-20 (Mar 2010) ISSN: 1573-2592 [Electronic] Netherlands
• PMID: 19890701 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cholinergic Agents
• Collagen Type II
• Cytokines
• HMGB1 Protein
• Receptors, Nicotinic
• Nicotine

Topics

• Animals
• Arthritis, Experimental (blood, chemically induced, immunology, physiopathology)
• Cattle
• Cholinergic Agents (administration & dosage)
• Collagen Type II (administration & dosage)
• Cytokines (antagonists & inhibitors, blood)
• Disease Progression
• HMGB1 Protein (antagonists & inhibitors)
• Inflammation
• Male
• Mice
• Mice, Inbred DBA
• Nicotine (administration & dosage)
• Receptors, Nicotinic (metabolism)
• Synovial Membrane (pathology)
• Vagotomy
• Vagus Nerve (drug effects, immunology, surgery)