1,25-dihydroxyvitamin D-3 treatment decreases macrophage accumulation in the CNS elf mice with experimental autoimmune encephalomyelitis

Sunlight, which is required for vitamin D biosynthesis, may be protective i n multiple sclerosis (MS), due to the immunoregulatory functions of 1,25-di hydroxyvitamin D-3 (1,25-(OH)(2)D-3), the hormonally active vitamin D metab olite. This hypothesis provided the impetus for the experiments reported he re investigating mechanisms whereby 1,25-(OH)(2)D-3 may inhibit murine expe rimental autoimmune encephalomyelitis (EAE). Severe EAE was induced, 1,25-( OH)(2)D-3 or mock treatment was administered, and clinical disease, histopa thological disease, and encephalitogenic cells in the central nervous syste m (CNS) were analyzed within 24-72 h of the treatment. The mock-treated mic e remained paralyzed (stage 3 EAE) while most hormone-treated animals regai ned the partial use of both hind limbs (stage 2 EAE) within 72 h of treatme nt. A histopathological examination showed the hormone-treated mice had a 5 0% decrease in white matter and meningeal inflammation at 72 h post treatme nt. 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 ab out 7.0 +/- 2.3 million Mac-1(+) cells/cord, whereas the hormone-treated mi ce had about 2.1 +/- 2.6 million Mac-1(+) cells/cord, which was not signifi cantly different from the unmanipulated control mice. Otherwise, the flow c ytometric analysis detected no significant differences between the groups w ith respect to CD4(+) or CD8(+) T cells or B cells or macrophages in draini ng lymph nodes or spinal cords. These results are discussed with regard to possible fates for the 5 million Mac-1(+) cells that were rapidly lost from the inflamed CNS in the 1,25-(OH)(2)D-3-treated mice, and the possible ben eficial effect of hormone treatment in resolving acute MS. (C) 2000 Elsevie r Science B.V. All rights reserved.