Enhancement of 1,25-dihydroxyvitamin D3-mediated suppression of experimental autoimmune encephalomyelitis by calcitonin.
The active form of vitamin D, 1alpha,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)], suppresses disease development in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS). However, complete disease prevention only occurs with doses that dramatically elevate serum calcium levels, thus limiting the usefulness of 1,25(OH)(2)D(3) as a potential MS therapeutic agent. Because calcitonin (CT) is believed to be released by hypercalcemia and has been shown to be anti-inflammatory, we examined whether suppression of EAE by 1,25(OH)(2)D(3) could be mediated either in part or entirely by CT. Continuous administration of pharmacological doses of CT did not prevent EAE. However, a combination of CT and a subtherapeutic dose of 1,25(OH)(2)D(3) additively suppressed EAE without causing hypercalcemia. Moreover, CT decreased the dose of 1,25(OH)(2)D(3) required for disease suppression. Our results suggest that CT may be a significant factor but cannot account entirely for 1,25(OH)(2)D(3)-mediated suppression of EAE.
Becklund
Bryan R
BR
Department of Biochemistry, University of Wisconsin, Madison, WI 53706-1544.
Hansen
Donald W
DW
Deluca
Hector F
HF
D000818:Animals; D002116:Calcitonin / Q000494:pharmacology* / Q000627:therapeutic use; D002118:Calcium / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000517:prevention & control; D006934:Hypercalcemia; D051379:Mice; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
C118756:dihydroxy-vitamin D3; D014807:Vitamin D; D002116:Calcitonin; D002118:Calcium