Enhancement of 1,25-dihydroxyvitamin D₃-mediated suppression of experimental autoimmune encephalomyelitis by calcitonin

The active form of vitamin D, 1α,25-dihydroxyvitamin D₃ [1,25(OH)₂D₃], 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)₂D₃ 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)₂D₃ 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)₂D₃ additively suppressed EAE without causing hypercalcemia. Moreover, CT decreased the dose of 1,25(OH)₂D₃ required for disease suppression. Our results suggest that CT may be a significant factor but cannot account entirely for 1,25(OH)₂D₃-mediated suppression of EAE.