Smoking worsens multiple sclerosis prognosis: Two different pathways are involved

•Smoking is a risk factor for early conversion to clinically definite MS.•Disease progression is more rapid in smoker MS patients compared to non-smokers.•Indoleamine 2,3-dioxygenase activity is reduced in MS patients who smoke.•Activity of renin-angiotensin system is increased in MS patients who smoke.•Smoking led to increased number of IL-6, IL-13, IL-17 and IL-22 producing cells.

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 risk.