1,25-Dihydroxyvitamin D3 attenuates the expression of experimental murine lupus of MRL/l mice.
The murine strain MRL/l spontaneously develops a systemic lupus erythematosus (SLE)-like syndrome. An increased number of T cells and polyclonal T helper cell activity has been described in these mice suggesting a potential role for 1,25-dihydroxyvitamin-D3 [1,25-D3], an antiproliferative hormone selecting the T-helper lymphocyte subset. One month old MRL/l mice were submitted or not to 1,25-D3 0.1 microgram for 4 weeks, then 0.15 microgram given i.p. every other day for 18 weeks while maintained on a low calcium chow. Dermatologic lesions, i.e. alopecia, necrosis of the ear and scab formation, were completely inhibited by 1,25-D3 therapy. By 20 weeks, all mice had developed proteinuria. However, the degree of proteinuria was somewhat reduced in treated mice as assessed by urine protein/creatine ratios (less than 4 vs greater than 4 in treated vs untreated mice respectively). Moreover, a trend for a reduction in serum titers for anti-ssDNA antibodies was observed at 18 weeks. The active vitamin D metabolite had no effect on the development of the generalized lymphoid hyperplasia. Hypercalcemia developed when 1,25-D3 was increased to 0.15 microgram (2.62 +/- 0.12 vs 1.97 +/- 0.07 mmol/l, treated vs untreated mice respectively). These results suggest a beneficial role of 1,25-D3 in the prevention or attenuation of some manifestations of murine SLE, a model sharing many immunologic features with human SLE.
Lemire
J M
JM
Department of Pediatrics, University of Texas Medical School of Houston.
Ince
A
A
Takashima
M
M
D000818:Animals; D000974:Antibodies, Antinuclear / Q000032:analysis; D002117:Calcitriol / Q000627:therapeutic use*; D002118:Calcium / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D008180:Lupus Erythematosus, Systemic / Q000517:prevention & control*; D051379:Mice; D008815:Mice, Inbred Strains; D011507:Proteinuria / Q000517:prevention & control
D000974:Antibodies, Antinuclear; D002117:Calcitriol; D002118:Calcium