期刊
JOURNAL OF NEUROIMMUNOLOGY
卷 103, 期 2, 页码 171-179出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/S0165-5728(99)00247-7
关键词
vitamin D; autoimmunity; macrophages; EAE; multiple sclerosis
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-3 (1,25-(OH)(2)D-3), the hormonally active vitamin D metabolite. This hypothesis provided the impetus for the experiments reported here investigating mechanisms whereby 1,25-(OH)(2)D-3 may inhibit murine experimental autoimmune encephalomyelitis (EAE). Severe EAE was induced, 1,25-(OH)(2)D-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 +/- 2.3 million Mac-1(+) cells/cord, whereas the hormone-treated mice had about 2.1 +/- 2.6 million Mac-1(+) 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(+) or CD8(+) 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(+) cells that were rapidly lost from the inflamed CNS in the 1,25-(OH)(2)D-3-treated mice, and the possible beneficial effect of hormone treatment in resolving acute MS. (C) 2000 Elsevier Science B.V. All rights reserved.
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