In vivo upregulation of interleukin-4 is one mechanism underlying the immunoregulatory effects of 1,25-dihydroxyvitamin D(3).
The active form of vitamin D (1,25-(OH)(2)D(3)) is a potent immune system regulator. In vivo the oral administration of 1, 25-(OH)(2)D(3) completely prevents experimental autoimmune encephalomyelitis (EAE), significantly prolongs allograft survival, and prevents collagen-induced arthritis. 1,25-(OH)(2)D(3) given to mice increased IL-4 protein and transcript levels. We have now tested the efficacy of 1,25-(OH)(2)D(3) on EAE development and allograft survival in IL-4-deficient [knockout (ko)] mice. 1, 25-(OH)(2)D(3) was found to be much less effective in the absence of IL-4, suggesting that IL-4 production is a significant factor in the action of 1,25-(OH)(2)D(3) on the immune system.
Cantorna
M T
MT
Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
Humpal-Winter
J
J
DeLuca
H F
HF
D000284:Administration, Oral; D000818:Animals; D001168:Arthritis / Q000139:chemically induced / Q000517:prevention & control; D002117:Calcitriol / Q000008:administration & dosage / Q000276:immunology* / Q000494:pharmacology* / Q000627:therapeutic use; D003094:Collagen / Q000494:pharmacology; D004198:Disease Susceptibility / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology / Q000401:mortality / Q000517:prevention & control; D005260:Female; D017353:Gene Deletion; D006085:Graft Survival / Q000187:drug effects / Q000276:immunology; D006183:H-2 Antigens / Q000276:immunology; D015847:Interleukin-4 / Q000172:deficiency / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012008:Recurrence; D014184:Transplantation, Homologous / Q000276:immunology; D015854:Up-Regulation / Q000187:drug effects*
D006183:H-2 Antigens; D012333:RNA, Messenger; D015847:Interleukin-4; D003094:Collagen; D002117:Calcitriol