2015 Apr 15;281:23-34. doi: 10.1016/j.jneuroim.2015.03.006. Epub 2015 Mar 6.
Smoking worsens multiple sclerosis prognosis: Two different pathways are involved.
Smoking worsens multiple sclerosis
(MS) prognosis. Our study provides evidence that indoleamine
2,3-dioxygenase activity is reduced in MS patients who smoke, leading to
increased production of IL-6 and IL-13. Additionally, both degree of
expression and renin-angiotensin system activity levels were increased
in MS patients who smoked, inducing increase in IL-17 and
IL-22-producing cell numbers as well as significantly greater production
of CCL2, CCL3 and CXCL10 chemokines by monocytes. Finally, both
pathways contributed to a significant decrease in the number of
CD4+CD25+FoxP3+ regulatory T cells in MS patients who smoked. Both
pathways could be responsible for the association between smoking and MS
IL-6 is pro-inflammatory cytokine, whilst IL-17 and -22 cooperatively potentiate proinflammatory effects. Regulatory T cells are key elements in immune self-tolerance and control of the autoreactive immune response.
Smoking is a risk factor for early conversion to definite MS as well as for worse prognosis
This is a story of risk factors; ask yourself why smoking matters? Let's take general health, the major risk factors for heart failure are hypertension (66%), followed by smoking (51%), whilst for lung cancer the odds ratio (the odds that an outcome will occur given a particular exposure) is 40.4. If we put this into perspective with other risk factors reported in MS: infectious mononucleosis (EBV) odds ratio 2.0; vitamin D<20ng/ml odds ratio 2.0, HLA-DRB1*15 odds ratio 2.0, and high salt-intake odds ratio 2.0. Not surprisingly the odds ratio for smoking and MS is also 2.0!
Individually these risk factors don't amount to much, but identifying these risk factors and figuring out how these factors increase the risk of MS or aggravate the autoimmunity is important. Also, they should form a decisive part of MS treatment strategies.
Labels: Autoimmuity, IL-6, Progression, smoking, Tregs