1,25-dihydroxyvitamin D3 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 D3 (1,25-(OH)2D3), the hormonally active vitamin D metabolite. This hypothesis provided the impetus for the experiments reported here investigating mechanisms whereby 1,25-(OH)2D3 may inhibit murine experimental autoimmune encephalomyelitis (EAE). Severe EAE was induced, 1,25-(OH)2D3 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)2D3-treated mice, and the possible beneficial effect of hormone treatment in resolving acute MS.
Nashold
F E
FE
Department of Biochemistry, University of Wisconsin-Madison, 53706, USA.
Miller
D J
DJ
Hayes
C E
CE
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002117:Calcitriol / Q000627:therapeutic use*; D002452:Cell Count / Q000187:drug effects; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D005260:Female; D005434:Flow Cytometry; D006614:Hindlimb / Q000503:physiopathology; D008198:Lymph Nodes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D016177:Macrophage-1 Antigen / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D010243:Paralysis / Q000175:diagnosis / Q000188:drug therapy; D013116:Spinal Cord / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology
D016177:Macrophage-1 Antigen; D002117:Calcitriol