1,25 Dihydroxyvitamin D[sub.3] Exerts Regional Effects in the Central Nervous System during Experimental Allergic Encephalomyelitis

1,25-dihydroxyvitamin D[sub.3] (1,25-D[sub.3]) is already known to prevent clinical signs of experimental allergic encephalomyelitis when animals are treated during the immunization phase. In the present work we have evaluated the ability of 1,25-D[sub.3] to inhibit chronic relapsing experimental al...

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Published inJournal of neuropathology and experimental neurology Vol. 55; no. 8; p. 904
Main Authors Nataf, S, Garcion, E, Darcy, F, Chabannes, D, Muller, J.Y, Brachet, P
Format Journal Article
LanguageEnglish
Published Oxford University Press 01.08.1996
Subjects
Analysis
Central nervous system
Encephalomyelitis
Multiple sclerosis
Vitamin D
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Summary:1,25-dihydroxyvitamin D[sub.3] (1,25-D[sub.3]) is already known to prevent clinical signs of experimental allergic encephalomyelitis when animals are treated during the immunization phase. In the present work we have evaluated the ability of 1,25-D[sub.3] to inhibit chronic relapsing experimental allergic encephalomylitis (EAE) of the Lewis rat, when administered after the beginning of clinical signs. We observed a significant clinical improvement in 1,25-D[sub.3]-treated rats. This effect was accompanied by a profound inhibition of CD4 antigen expression by central nervous system (CNS) infiltrating monocytes/macrophages and parenchymal microglia. In addition, immunohistochemical analysis performed at the time of the second attack evidenced a region-specific distribution of inflammatory cells. In the same way, some aspects of the effects exerted by 1,25-D[sub.3] appeared to vary depending on the region considered, namely spinal cord, brainstem, cerebellum, midbrain or anterior brain. Thus, in 1,25-D[sub.3]-treated rats, we observed an almost complete inhibition of CD4 antigen expression in the granule cell layer and the adjacent white matter of the cerebellum as well as a marked decrease in the number of OX42-positive cells (macrophages and activated microglia) in anterior brain sections. We conclude that 1,25-D[sub.3] can exert immunomodulatory effects inside the CNS during an ongoing immune process and may thus represent a promising therapy for multiple sclerosis. Keywords: Calcitriol, CD4 antigen, Encephalomyelitis, Lymphocyte, Microglia, Multiple sclerosis, Vitamin D
ISSN:0022-3069
DOI:10.1097/00005072-199608000-00006