A VITAMIN-D ANALOG (MC-1288) HAS IMMUNOMODULATORY PROPERTIES AND SUPPRESSES COLLAGEN-INDUCED ARTHRITIS (CIA) WITHOUT CAUSING HYPERCALCEMIA

The immunomodulatory properties of the vitamin D analogue MC 1288 (20- epi-1 alpha,25-dihydroxycholecalciferol) were investigated in CIA in r ats. The analogue was administered systemically at three different tim e points; (i) for 10 consecutive days before collagen(CII) immunizatio n; (ii) for 10 consecutive days after CII immunization; or (iii) for 7 consecutive days from disease onset. Treatment initiated either 10 da ys before CII immunization or at the day of collagen immunization effe ctively suppressed the development of arthritis. Treatment initiated a t the day of the onset of arthritis reduced the severity of joint infl ammation. Significantly, doses which did not induce hypercalcaemia dec reased the incidence and severity of arthritis. In vivo treatment with the 20-epi analogue of 1 alpha,25-dihydroxycholecalciferol diminished the serum levels of antibodies to rat CII. Similarly, mitogen-induced proliferation of lymph node cells from rat CII-immunized animals was reduced. The experiments demonstrate that the vitamin D analogue MC 12 88 has the ability to prevent, and furthermore to suppress, already es tablished CIA by its immunomodulatory properties without inducing hype rcalcaemia.