RESUMEN
Previously we demonstrated that 1,25-dihydroxyvitamin D3 blocks the progression of relapsing encephalomyelitis. We now propose that 1,25-dihydroxyvitamin D3 blocks these autoimmune symptoms by stimulating the differentiation and/or function of cells that inhibit the encephalitogenic process. To support this belief, we have found that 1,25-dihydroxyvitamin D3 administration to mice increases IL-4 transcripts by 3- to 25-fold and TGF-beta 1 transcripts by 4- to 24-fold. Similarly, IL-4 and TGF-beta 1 transcripts were higher in the central nervous system of 1,25-dihydroxyvitamin D3-treated mice compared with controls. The number of cells recoverable from the lymph nodes of 1,25-dihydroxyvitamin D3-treated mice was only 50% that of controls. Overall, 1,25-dihydroxyvitamin D3 treatment causes a net loss in the total number of lymphocytes while the number of IL-4 and TGF-beta 1 transcripts increased. The systemic and local increase in the expression of these two anti-inflammatory cytokines by 1,25-dihydroxyvitamin D3 may be responsible for the ability of this drug to block encephalomyelitis.
Asunto(s)
Adyuvantes Inmunológicos/farmacología , Calcitriol/farmacología , Encefalomielitis Autoinmune Experimental/inmunología , Encefalomielitis Autoinmune Experimental/prevención & control , Interleucina-4/fisiología , Factor de Crecimiento Transformador beta/fisiología , Adyuvantes Inmunológicos/administración & dosificación , Administración Oral , Animales , Calcitriol/administración & dosificación , Células Cultivadas , Encefalomielitis Autoinmune Experimental/patología , Femenino , Interferón gamma/metabolismo , Interleucina-4/genética , Ganglios Linfáticos/patología , Recuento de Linfocitos , Masculino , Ratones , Ratones Endogámicos C57BL , Médula Espinal/patología , Transcripción Genética/efectos de los fármacos , Factor de Crecimiento Transformador beta/genética , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
1. Female rats fed on a vitamin D deplete (D-) diet for 90 days prior to mating gave birth to litters having significantly fewer young than females fed a diet containing vitamin D (2.2 IU/g, D + diet). 2. Neither age nor body weight of females had a significant influence on litter size. 3. Serum calcium and phosphorus levels in D+ and D- dams were not significantly different, nor were serum calcium and phosphorus levels and bone ash of D+ and D- weanlings. 4. The level of 25-hydroxyvitamin D3 [25(OH)D3], the main circulating form of vitamin D, was low in D- dams and was not detected in D- weanlings. 5. These data suggest that vitamin D is required for reproduction in the rat.