Selective resistance to different glucocorticoids in severe autoimmune disorders

Ilenia Drigo, Elisa Piscianz, Erica Valencic, Sara De Iudicibus, Alberto Tommasini, Alessandro Ventura, Giuliana Decorti

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)313-319
Number of pages7
JournalClinical Immunology
Volume134
Issue number3
DOIs
Publication statusPublished - Mar 2010

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Keywords

  • Betamethasone
  • Glucocorticoids
  • Inflammatory diseases
  • Methylprednisolone
  • Multidrug Resistance-related Protein 1
  • P-glycoprotein
  • Resistance

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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