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Smoking worsens multiple sclerosis prognosis: Two different pathways are involved

      Highlights

      • 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.

      Abstract

      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.

      Abbreviations:

      3-HAA (3-hydroxyanthranilic acid), ACE (angiotensin-converting enzyme), APCs (antigen presenting cells), Ang (angiotensin), ATR1 (angiotensin type 1 receptor), CIS (clinically isolated syndrome), CDMS (clinically definite multiple sclerosis), CNS (central nervous system), DCs (dendritic cells), EAE (experimental autoimmune encephalomyelitis), EDSS (expanded disability status scale), GAPDH (glyceraldehyde-3-phosphate dehydrogenase), IDO (indoleamine 2,3-dioxygenase), Kyn (kynurenine), LPS (lipopolysaccharide), MBP (myelin basic protein), MS (multiple sclerosis), NAT1 (N-acetyltransferase 1), NO (nitric oxide), PBMCs (peripheral blood mononuclear cells), PHA (phytohemagglutinin), poly (I:C) (polyinosinic–polycytidylic acid), RAS (renin–angiotensin system), RIA (radio immune assay), ROS (reactive oxygen species), RRMS (relapsing remitting multiple sclerosis), SPMS (secondary progressive multiple sclerosis), TCLs (T cell lines), TLR (Toll-like receptor), Try (tryptophan)

      Keywords

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