Selective resistance to different glucocorticoids in severe autoimmune disorders |
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| Authors: | Ilenia Drigo Elisa Piscianz Erica Valencic Sara De Iudicibus Alberto Tommasini Alessandro Ventura Giuliana Decorti |
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| Affiliation: | 1. Cellular and Molecular Endocrine Research Center and Obesity Research Center, Research Institute for Endocrine Sciences (RIES), Shahid Beheshti University of Medical Sciences, Tehran, Iran;2. Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences (RIES), Shahid Beheshti University of Medical Sciences, Tehran, Iran;3. Endocrine Physiology Research Center, Research Institute for Endocrine Sciences (RIES), Shahid Beheshti University of Medical Sciences, Tehran, Iran;1. GlaxoSmithKline, Stevenage, United Kingdom;2. GlaxoSmithKline, Uxbridge, United Kingdom;3. Refractory Respiratory Inflammation Discovery Performance Unit, GlaxoSmithKline, Stevenage, United Kingdom;1. Laboratory of Experimental Hepatology and Drug Targeting (HEVEFARM), IBSAL, University of Salamanca, Salamanca, Spain;2. University Hospital of Salamanca, IECSCYL-IBSAL, Salamanca, Spain;3. Instituto de Investigaciones Farmacologicas, Facultad de Farmacia y Bioquimica, CONICET, Universidad de Buenos Aires, Buenos Aires, Argentina;4. CIBERehd, Instituto de Salud Carlos III, Madrid, Spain |
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| Abstract: | Resistance to glucocorticoids often occurs in patients with severe inflammatory disorders. Occasionally, this resistance could be overcome by switching to a different glucocorticoid, but the mechanisms of this selectivity are not clear. We studied this condition in three patients with severe inflammatory disorders, who responded satisfactorily to betamethasone, but could not be switched to equipotent doses of methylprednisolone or prednisone. While betamethasone displayed similar activity on lymphocyte proliferation in cells obtained from the three patients and controls, higher concentrations of methylprednisolone were needed to inhibit proliferation in patients' cells. In a competition study, the concentration of methylprednisolone that inhibited 50% of specific [3H]dexamethasone binding was increased in patients' lymphocytes. Higher Rhodamine-123 efflux was demonstrated in CD4 T cells from two patients, suggesting that an increased activity of membrane transporters could be responsible for the selective response to different glucocorticoids, even if P-glycoprotein and MRP1 expression was not increased. |
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