1,25-Dihydroxyvitamin D sub(3) treatment decreases macrophage accumulation in the CNS of mice with experimental autoimmune encephalomyelitis

Sunlight, which is required for vitamin D biosynthesis, may be protective in multiple sclerosis (MS), due to the immunoregulatory functions of 1,25-dihydroxyvitamin D sub(3) (1,25-(OH) sub(2)D sub(3)), the hormonally active vitamin D metabolite. This hypothesis provided the impetus for the experiments reported here investigating mechanisms whereby 1,25-(OH) sub(2)D sub(3) may inhibit murine experimental autoimmune encephalomyelitis (EAE). Severe EAE was induced, 1,25-(OH) sub(2)D sub(3) or mock treatment was administered, and clinical disease, histopathological disease, and encephalitogenic cells in the central nervous system (CNS) were analyzed within 24-72 h of the treatment. The mock-treated mice remained paralyzed (stage 3 EAE) while most hormone-treated animals regained the partial use of both hind limbs (stage 2 EAE) within 72 h of treatment. A histopathological examination showed the hormone-treated mice had a 50% decrease in white matter and meningeal inflammation at 72 h post treatment. A flow cytometric analysis of cell surface markers on spinal cord cells recovered 24 h post treatment showed the mock-treated mice with EAE had about 7.0 plus or minus 2.3 million Mac-1 super(+) cells/cord, whereas the hormone-treated mice had about 2.1 plus or minus 2.6 million Mac-1 super(+) cells/cord, which was not significantly different from the unmanipulated control mice. Otherwise, the flow cytometric analysis detected no significant differences between the groups with respect to CD4 super(+) or CD8 super(+) T cells or B cells or macrophages in draining lymph nodes or spinal cords. These results are discussed with regard to possible fates for the 5 million Mac-1 super(+) cells that were rapidly lost from the inflamed CNS in the 1,25-(OH) sub(2)D sub(3)-treated mice, and the possible beneficial effect of hormone treatment in resolving acute MS.