Glucocorticoids and interferon-α in the acquired immunodeficiency syndrome

Guido Norbiato, Maurizio Bevilacqua, Tarcisio Vago, Mario Clerici

Research output: Contribution to journalArticlepeer-review

Abstract

Some patients with acquired immunodeficiency syndrome (AIDS) develop glucocorticoid resistance characterized by low receptor affinity (K(d)) for glucocorticoids in mononuclear cells and high values of ACTH and cortisol. As glucocorticoids regulate interferon-α (IFNα) production, we hypothesized that IFNα, a cytokine produced predominantly by monocytes in AIDS, should be increased in cortisol-resistant AIDS, attributing the lack of cortisol inhibition to IFNα production. Therefore, we examined glucocorticoid receptor characteristics on monocytes by [3H]dexamethasone binding and measured IFNα, cortisol, and ACTH in AIDS patients with (AIDS-GR) or without glucocorticoid resistance (AIDS-C) and controls (C). Monocytes of AIDS-GR patients had a receptor K(d) of 10.5 ± 4.2 nmol/L that was higher than that in the AIDS-C group (2.9 ± 0.8 nmol/L) and normal subjects (2.0 ± 0.8 nmol/L; P <0.01). IFNα levels were increased in the AIDS-GR group (17 ± 6 vs. 4 ± 1 U/mL in the AIDS-C group and 2 ± 0.5 U/mL in the C group; P <0.01). Correlations were found between plasma IFNα and receptor K(d) on monocytes of AIDS-GR (r = 0.77) and between IFNα and plasma cortisol in the same group (r = 0.74). The poly(I)-poly(C)-induced IFNα production by monocytes was inhibited by glucocorticoids in the C and AIDS-C groups (~80% inhibition in both groups); the effect was reversed by the receptor antagonist RU-38486. By contrast, glucocorticoids failed to inhibit IFNα production from AIDS-GR monocytes (~20% inhibition). In conclusion, elevated IFNα levels in AIDS-GR may be due to the lack of inhibitory effect of cortisol on IFNα production due to cortisol resistance in monocytes.

Original languageEnglish
Pages (from-to)2601-2606
Number of pages6
JournalJournal of Clinical Endocrinology and Metabolism
Volume81
Issue number7
DOIs
Publication statusPublished - 1996

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

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