Synergistic inhibitory effect of cyclosporin A and vitamin D derivatives on T-lymphocyte proliferation in active ulcerative colitis

The American Journal of Gastroenterology
Maria StioAndrea G Bonanomi

Abstract

1,25-Dihydroxyvitamin D3 [1,25(OH)2D3], the hormonal active form of vitamin D3, could represent a potentially therapeutic agent in autoimmune diseases. Cyclosporin A (CsA) shows immunoregulatory properties, which, in many respects, seem to be similar to those of 1,25(OH)2D3. Our aim was to investigate the possible synergistic effect exerted by CsA in combination with 1,25(OH)2D3 or its nonhypercalcemic analogues, EB 1089 and KH 1060, on the proliferative response of T lymphocytes obtained from active ulcerative colitis patients. The T lymphocyte-enriched population was treated with phytohemagglutinin and CsA (doses from 1 ng to 1000 ng/ml) alone or in association with 1,25(OH)2D3 or EB 1089 or KH 1060 (0.1, 1, 10 nM final concentration). Cell proliferation was determined by [3H]thymidine incorporation and analyzed on day 5 of culture. After incubation with CsA, T lymphocyte proliferation was significantly inhibited in comparison with the vehicle-treated cultures. However, T lymphocytes from ulcerative colitis patients were significantly more sensitive to CsA than those from healthy controls. The inhibition in T lymphocyte proliferation, after treatment of the cultures with CsA associated with either 1,25(OH)2D3 or EB 1089 or KH...Continue Reading

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Citations

Nov 3, 2005·Nature Clinical Practice. Gastroenterology & Hepatology·Wee-Chian LimYan Chun Li
Feb 28, 2008·Current Opinion in Gastroenterology·Helen M PappaRichard J Grand
Feb 15, 2011·Therapeutic Advances in Gastroenterology·Maitreyi RamanSubrata Ghosh
Feb 16, 2005·International Immunopharmacology·Maria StioAndrea G Bonanomi
Mar 19, 2014·Journal of Crohn's & Colitis·Maria MartinesiMaria Stio
Oct 8, 2016·Cancer Biology & Therapy·Kristine C OlsonThomas P Loughran

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