1,25-DIHYDROXYVITAMIN-D-3 EXERTS REGIONAL EFFECTS IN THE CENTRAL-NERVOUS-SYSTEM DURING EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS

1,25-dihydroxyvitamin D-3 (1,25-D-3) is already known to prevent clini cal signs of experimental allergic encephalomyelitis when animals are treated during the immunization phase. In the present work we have eva luated the ability of 1,25-D-3 to inhibit chronic relapsing experiment al allergic encephalomylitis (EAE) of the Lewis rat, when administered after the beginning of clinical signs. We observed a significant clin ical improvement in 1,25-D-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 micro glia. In addition, immunohistochemical analysis performed at the time of the second attack evidenced a region-specific distribution of infla mmatory cells. In the same way, some aspects of the effects exerted by 1,25-D-3 appeared to vary depending on the region considered, namely spinal cord, brainstem, cerebellum, midbrain or anterior brain. Thus, in 1,25-D-3-treated rats, we observed an almost complete inhibition of CD4 antigen expression in the granule cell layer and the adjacent whi te matter of the cerebellum as well as a marked decrease in the number of OX42-positive cells (macrophages and activated microglia) in anter ior brain sections. We conclude that 1,25-D-3 can exert immunomodulato ry effects inside the CNS during an ongoing immune process and may thu s represent a promising therapy for multiplesclerosis.