Multiple Sclerosis Society of Canada

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MS Society-funded study shows that nicotine reduces the invasion of harmful immune cells into the brain in mice with an MS-like disease

  • Canadian Study
  • MS Society Funded
Background

A substantial body of evidence suggests that smoking tobacco increases the risk of developing multiple sclerosis (MS) and may even accelerate disease progression. On the other hand, nicotine, the ingredient in tobacco responsible for its addictive properties, has been shown to have anti-inflammatory properties when studied separately from the other ingredients of smoked tobacco. With support from an operating grant from the MS Society of Canada, Dr. Alain Simard (Université de Moncton, Moncton, New Brunswick) and collaborators have been studying nicotinic acetylcholine receptors, a family of proteins found on the surface of immune cells that are activated by nicotine and other similar molecules. They hypothesize that nicotine may be able to control the invasion of certain types of immune cells into the central nervous system (CNS) in people living with MS.

Among these specialized immune cells are neutrophils and monocytes. Under normal circumstances these cells circulate in the blood and migrate into tissues such as the brain and spinal cord when called upon to fight infection. In the MS brain, neutrophils and monocytes have been found in active lesions or sites of damage, and they are widely thought to contribute to the development and progression of MS.

In their study, published online in the Journal of Immunology, Dr. Simard and his research team explore whether nicotine can counter the pro-inflammatory effects of neutrophils and monocytes in mice with an MS-like disease. The study was jointly funded by the MS Society of Canada and the New Brunswick Health Research Foundation.

The Study

In their study, Dr. Simard and his team placed a micro-pump under the skin of mice with an MS-like disease; this pump delivered small amounts of nicotine to the animal on a continual basis. The effect of the nicotine on the animal’s overall level of disability (tail and limb paralysis, as well as time to recovery) over time was tested and compared to mice who received a mock solution. The research team also assessed whether nicotine affected the number of pro-inflammatory neutrophils and monocytes in the animal’s blood, brain, and spinal cord.

In another set of experiments, the researchers measured nicotine’s ability to interfere with the production of two chemokines, CCL2 and CXCL2, in animals with MS-like disease. Chemokines are small beacon molecules that draw immune cells to sites of inflammation. CCL2 and CXCL2 attract pro-inflammatory monocytes and neutrophils, respectively.

Results

Nicotine reduced clinical symptoms in mice with an MS-like disorder compared to mice who received a mock treatment; the disorder became less severe in the nicotine-treated group, and these mice had an improved recovery time. Upon closer inspection, administration of nicotine decreased the number of pro-inflammatory monocytes in the animal’s bloodstream. Nicotine also decreased the number of pro-inflammatory monocytes and neutrophils, entering the brain and spinal cord.

At a molecular level, nicotine blocked the production of two chemokines present in the animal’s brain; the chemokine CCL2, used to recruit monocytes, and the chemokine CXCL2, responsible for attracting neutrophils.

Comment

Nicotine, through its activation of nicotinic acetycholine receptors, is capable of alleviating disability symptoms in mice with an MS-like disease. This is accomplished, in part, by the drug’s ability to reduce the number of pro-inflammatory monocytes and neutrophils that infiltrate the brain and spinal cord. The authors conclude that this decrease may be due to the lack of CCL2 and CXCL2 in the animal’s brain, chemical beacons whose production is blocked by nicotine.

Nicotine is an ingredient of tobacco products such as cigarettes, which are considered a major risk factor for MS. The nicotine used in this study was devoid of other chemicals normally found in cigarettes. These observations support the findings of an earlier Swedish study in which cigarette smoking was associated with greater MS risk, but also showed that chewable tobacco was associated with lower risk, suggesting that factors in smoked tobacco other than nicotine may be contributing to MS risk.

Future studies will further explore other substances that are chemically similar to nicotine, which activate nicotinic acetylcholine receptors, as a potential therapeutic direction for treating MS.

Source

Jiang W et al. (2016). Infiltration of CCR2+Ly6Chigh proinflammatory monocytes and neutrophils into the central nervous system are modulated by nicotinic acetylcholine receptors in a model of multiple sclerosis. Journal of Immunology. doi:10.4049/jimmunol.1501613 [epub ahead of print].