Short term fingolimod treatment decreases soluble VLA 4 levels in MS patients

Multiple sclerosis (MS) is an immune mediated disorder of the central nervous system. T-cells and other immune effector cells play crucial roles in MS pathogenesis by crossing the brain–blood barrier and consequently destroying the myelin sheat and axons. Fingolimod (FTY720) is an oral sphingosine-1-phosphate (S1P) receptor modulator, approved for treatment of MS. Resting T and B lymphocytes express elevated levels of S1P receptor and lymphocyte migration from the lymphoid organs to the brain depends on the activity of this receptor. Recent evidence suggests that fingolimod does not only prevent lymphocyte migration to the central nervous system but also exhibit other mechanisms of action. To investigate the potential effector functions of fingolimod on cytokine, chemokine and soluble adhesion molecule production, levels of IL-17A, IL-10, IL-6, IL-13, IFN-γ, TNFα, IL-4, IL-12p40, soluble VLA4 (sVLA4), sVCAM1, sICAM, CXCL13, CCL2 and IL-8 were measured by ELISA in sera obtained before (S0) and three months after the onset (S3m) of fingolimod treatment in 10 MS patients. Serum sVLA4 levels were significantly decreased in all MS patient’s sera after treatment and sVLA4 levels were significantly lower in S3m sera as compared to S0 sera. By contrast, levels of other examined factors did not show any statistical difference among S0 and S3m sera. These results suggest that in contrast with other immunomodulating agents, shortterm fingolimod treatment does not affect Th1 and Th17 immunities. Reduction of sVLA4 by fingolimod treatment may contribute to prevention of lymphocyte crossing through blood–brain barrier and thus amelioration of MS symptoms.