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Nicotinic Attenuation of Central Nervous System Inflammation and Autoimmunity¹

Fu-Dong Shi^2,*, Wen-Hua Piao^3,4,*, Yen-Ping Kuo^5,, Denise I. Campagnolo^*, Timothy L. Vollmer^6,* and Ronald J. Lukas²

^* Department of Neurology and Department of Neurobiology, Barrow Neurological Institute, St. Joseph’s Hospital and Medical Center, Phoenix, AZ 85013

The expression of nicotinic acetylcholine receptors by neurons, microglia, and astrocytes suggests possibly diverse mechanisms by which natural nicotinic cholinergic signaling and exposure to nicotine could modulate immune responses within the CNS. In this study, we show that nicotine exposure significantly delays and attenuates inflammatory and autoimmune responses to myelin Ags in the mouse experimental autoimmune encephalomyelitis model. In the periphery, nicotine exposure inhibits the proliferation of autoreactive T cells and alters the cytokine profile of helper T cells. In the CNS, nicotine exposure selectively reduces numbers of CD11c⁺ dendritic and CD11b⁺ infiltrating monocytes and resident microglial cells and down-regulates the expression of MHC class II, CD80, and CD86 molecules on these cells. The results underscore roles of nicotinic acetylcholine receptors and nicotinic cholinergic signaling in inflammatory and immune responses and suggest novel therapeutic options for the treatment of inflammatory and autoimmune disorders, including those that affect the CNS.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported in part by grants from Barrow Neurological Foundation and the National Institutes of Health (R01 AI052463). The contents of this report are solely the responsibility of the authors and do not necessarily represent the views of the aforementioned awarding agencies.

² Address correspondence and reprint requests to Dr. Fu-Dong Shi or Dr. Ronald J. Lukas, Barrow Neurological Institute, St. Joseph’s Hospital and Medical Center, 350 West Thomas Road, Phoenix, AZ 85013. E-mail addresses: Fu-Dong.Shi{at}chw.edu or rlukas{at}chw.edu

³ W.-H.P. and F.-D.S. contributed equally to this work.

⁴ Current address: Department of Clinical Laboratory, Ningxia People’s Hospital, Yinchuan, Ningxia Province, People’s Republic of China.

⁵ Current address: School of Osteopathic Medicine in Arizona, A. T. Still University, 5850 East Still Circle, Mesa, AZ 80206.

⁶ Current address: Department of Neurology, University of Colorado School of Medicine, Denver, CO 80045.

⁷ Abbreviations used in this paper: nAChR, nicotinic acetylcholine receptor; MS, multiple sclerosis; EAE, experimental autoimmune encephalomyelitis; MOG, myelin oligodendrocyte glycoprotein; PLP, proteolipid protein.