Cyclosporin A and vitamin D metabolism: studies in patients with psoriasis and in rats.

Abstract

1. Cyclosporin A, an immunosuppressive drug used to treat psoriasis, stimulates renal synthesis of 1,25-dihydroxyvitamin D in rats. 1,25-Dihydroxyvitamin D can also reduce the activity of psoriasis, and in the present study we have examined the possibility that cyclosporin A mediates some of its actions in psoriasis by renal or extra-renal production of 1,25-dihydroxyvitamin D. 2. Treatment of 12 psoriatic patients with cyclosporin A (5 mg day-1 kg-1) for 3 months significantly improved the psoriasis activity and severity index and reduced glomerular filtration rate, but serum 1,25-dihydroxyvitamin D levels were not changed. However, 1-3 months after stopping cyclosporin A treatment, an increase in the psoriasis activity and severity index score was accompanied by a small, but significant, increase in serum 1,25-dihydroxyvitamin D concentration. Plasma 1,25-dihydroxyvitamin D levels in rats gavaged with cyclosporin A (15 mg day-1 kg-1 for 2 weeks) were significantly increased compared with controls, but a lower dose of cyclosporin A (2.4 mg day-1 kg-1) had no effect. Renal 25-hydroxyvitamin D-24-hydroxylase activity in rat kidney homogenates was not different between control and cyclosporin A-treated rats. Renal 25-hydroxyvitamin D-1 alpha-hydroxylase activity was not detectable in these homogenates. Extra-renal production of 1,25-dihydroxyvitamin D by activated macrophages isolated from the synovial fluid of patients with inflammatory arthritis was reduced after incubation with cyclosporin A (0.1-10 mumol/l) for 30 h or 5 days.(ABSTRACT TRUNCATED AT 250 WORDS)

• Authors: A J Shaw, M E Hayes, M Davies, B D Edwards, F W Ballardie, R J Chalmers, E B Mawer
• Journal: Clinical science (London, England : 1979) (Clin Sci (Lond)) Vol. 86 Issue 5 Pg. 627-32 (May 1994) ISSN: 0143-5221 [Print] England
• PMID: 8033516 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cyclosporine
• Calcitriol

Topics

• Animals
• Arthritis (metabolism)
• Calcitriol (biosynthesis, blood, metabolism)
• Cells, Cultured
• Cyclosporine (pharmacology, therapeutic use)
• Glomerular Filtration Rate (drug effects)
• Humans
• Macrophages (drug effects, metabolism)
• Male
• Psoriasis (blood, drug therapy)
• Rats
• Rats, Wistar
• Synovial Fluid (metabolism)