High-dose vitamin D supplementation reduces IL-17-producing CD4+ T-cells and effector-memory CD4+ T-cells in multiple sclerosis patients (S38.001)

OBJECTIVE: To determine the effect of cholecalciferol supplementation on cytokine production and memory phenotype of CD4+ T-cells in multiple sclerosis (MS) patients. BACKGROUND: Vitamin D deficiency has been linked to increased risk for developing MS, as well as increased disease activity in established MS. Ex-vivo studies of lymphocytes from vitamin D supplemented MS patients are scarce, although it is a potent immunomodulator in vitro. DESIGN/METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from blood collected at baseline and 6 months in a randomized, double-blind trial of cholecalciferol supplementation in 32 MS patients (15 received high-dose (10,400 IU/day) and 17 low-dose (800 IU/day) cholecalciferol. After thawing, PBMCs were stimulated with anti-CD3/CD28 coated beads for 5 days, followed by PMA/Ionomycin for 4 hours to stimulate cytokine production. Immuno-staining was performed for cytokine and memory markers by flow-cytometry. RESULTS: Baseline demographic and immunological parameters were similar between the two groups. The high-dose group had a greater rise in serum 25-hydroxyvitamin D vs. baseline (33.67 vs 5.35 ng/mL, p<0.0001) at the end of the study. There was a decrease in the percentage of IL17+ CD4+ cells in the high-dose group (-3.27[percnt], p=0.027); no change was seen in the low-dose group (-0.21[percnt], p=0.738). The percentage of T-effector memory (Tem) cells decreased in the high-dose group (-10.4[percnt], p=0.013) but not in the low-dose group (-0.7[percnt], p=0.882). Reduced IL-17 production occurred primarily when the increase in serum 25-hydroxyvitamin D levels was above 20 ng/ml (-1.9[percnt] per 10 ng/ml increase, p=0.007). A strong correlation was noted between the decrease in Tem cells and IL-17+ CD4+ cells (Spearman9s rho=0.672, p<0.001). CONCLUSIONS: High-dose vitamin D supplementation reduced IL-17 producing CD4+ T-cells and CD4+ Tem cells in MS, an effect primarily observed in those with substantial increases in 25-hydroxyvitamin D levels. Study Supported by: NMSS FP-1787-01 to P.B. Disclosure: Dr. Bhargava has nothing to disclose. Dr. Sotirchos has nothing to disclose. Dr. Eckstein has received personal compensation for activities with Biogen Idec, Bayer Pharmaceuticals, and Pfizer Inc. Dr. Ntranos has nothing to disclose. Dr. Gocke has nothing to disclose. Dr. Mowry has received research support from Teva Neuroscience. Dr. Calabresi has received personal compensation for activities with Abbott, Vaccinex, and Vertex. Dr. Calabresi has received research support from Novartis and Biogen Idec.