title: Selective resistance to different glucocorticoids in severe autoimmune disorders.
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 [(3)H]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.
authors: Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste, Italy.
authors: Ilenia
authors: I
authors: Drigo
authors: Elisa
authors: E
authors: Piscianz
authors: Erica
authors: E
authors: Valencic
authors: Sara
authors: S
authors: De Iudicibus
authors: Alberto
authors: A
authors: Tommasini
authors: Alessandro
authors: A
authors: Ventura
authors: Giuliana
authors: G
authors: Decorti
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D001623:Betamethasone / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002648:Child; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004351:Drug Resistance; D005260:Female; D005434:Flow Cytometry; D005562:Formazans / Q000737:chemistry; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D007223:Infant; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D008775:Methylprednisolone / Q000627:therapeutic use; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011239:Prednisolone / Q000627:therapeutic use; D013778:Tetrazolium Salts / Q000737:chemistry; D055815:Young Adult
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D001623:Betamethasone; D004247:DNA; D005562:Formazans; D005938:Glucocorticoids; D008775:Methylprednisolone; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D011239:Prednisolone; D013778:Tetrazolium Salts; C079782:MTT formazan; C421109:multidrug resistance-associated protein 1