1,25-dihydroxyvitamin D3 is a positive regulator for the two anti-encephalitogenic cytokines TGF-beta 1 and IL-4.
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.
Cantorna
M T
MT
Department of Biochemistry, University of Wisconsin-Madison, College of Agricultural and Life Sciences 53706, USA.
Woodward
W D
WD
Hayes
C E
CE
DeLuca
H F
HF
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology*; D000284:Administration, Oral; D000818:Animals; D002117:Calcitriol / Q000008:administration & dosage / Q000494:pharmacology*; D002478:Cells, Cultured; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000235:genetics / Q000502:physiology*; D008198:Lymph Nodes / Q000473:pathology; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013116:Spinal Cord / Q000473:pathology; D014158:Transcription, Genetic / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000276:Adjuvants, Immunologic; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D007371:Interferon-gamma; D002117:Calcitriol