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.

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The effect of the ionophore RO 2-2985 on the efflux of calcium from the renal tubule was studied employing the in vivo microinjection technique. Microinjection solutions contained either RO 2-2985 (E) or its diluent (C). Following microinjections into the early proximal tubule, urinary 45Ca recoveries averaged 10.1 +/- 1.9 (C) and 3.5 +/- 1.4% (E) (P is less than 0.005), while recoveries averaged 32.3 +/- 6.9 (C) and 24.9 +/- 6.5% (E) (P is less than 0.05) following microinjections into the late proximal tubule. To determine if the decreased recovery of calcium was a specific effect, the effect of RO 2-2985 on the efflux of sodium, phosphate, and 3-O-methyl-D-glucose was examined. Compared to controls, RO2-2985 did not affect the urinary recoveries of 22Na, [32P]orthophosphoric acid, or 3-O-methyl-D-[14C]glucose. These studies demonstrate that RO 2-2985 enhances the efflux of calcium microinjected into the proximal portions of the rat nephron.