The vagus nerve and nicotinic receptors involve inhibition of HMGB1 release and early pro-inflammatory cytokines function in collagen-induced arthritis.
OBJECTIVE
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.
Li
Tong
T
Department of Rheumatology, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
Zuo
Xiaoxia
X
Zhou
Yaou
Y
Wang
Yanping
Y
Zhuang
Hanping
H
Zhang
Lingli
L
Zhang
Huali
H
Xiao
Xianzhong
X
D000818:Animals; D001169:Arthritis, Experimental / Q000097:blood / Q000139:chemically induced / Q000276:immunology* / Q000503:physiopathology; D002417:Cattle; D018678:Cholinergic Agents / Q000008:administration & dosage; D024043:Collagen Type II / Q000008:administration & dosage; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000097:blood; D018450:Disease Progression; D024243:HMGB1 Protein / Q000037:antagonists & inhibitors*; D007249:Inflammation; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D009538:Nicotine / Q000008:administration & dosage*; D011978:Receptors, Nicotinic / Q000378:metabolism*; D013583:Synovial Membrane / Q000473:pathology; D014628:Vagotomy; D014630:Vagus Nerve / Q000187:drug effects / Q000276:immunology* / Q000601:surgery
D018678:Cholinergic Agents; D024043:Collagen Type II; D016207:Cytokines; D024243:HMGB1 Protein; D011978:Receptors, Nicotinic; D009538:Nicotine