1,25-Dihydroxyvitamin D₃ is a positive regulator for the two anti- encephalitogenic cytokines TGF-β1 and IL-4

Previously we demonstrated that 1,25-dihydroxyvitamin D₃ blocks the progression of relapsing encephalomyelitis. We now propose that 1,25- dihydroxyvitamin D₃ blocks the progression of relapsing encephalomyelitis. We now propose that 1,25-dihydroxyvitamin D₃ blocks these autoimmune symptomes by stimulating the differentiation and/or function of cells that inhibit the encephalitogenic process. To support this belief, we have found that 1,25-dihydroxyvitamin D₃ administration to mice increases IL-4 transcripts by 3- to 25-fold and TGF-β1 transcripts by 4- to 24-fold. Similarly, IL-4 and TGF-β1 transcripts were higher in the central nervous system of 1,25-dihydroxyvitamin D₃-treated mice compared with controls. The number of cells recoverable from the lymph nodes of 1,25-dihydroxyvitamin D₃-treated mice was only 50% that of controls. Overall, 1,25- dihydroxyvitamin D₃ treatment causes a net loss in the total number of lymphocytes while the number of IL-4 and TGF-β1 transcripts increased. The systemic and local increase in the expression of these two anti-inflammatory cytokines by 1,25-dihydroxyvitamin D₃ may be responsible for the ability of this drug to block encephalomyelitis.