Glucocorticoids and interferon-α in the acquired immunodeficiency syndrome

Guido Norbiato, Maurizio Bevilacqua, Tarcisio Vago, Mario Clerici

Research output: Contribution to journalArticle

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

Fingerprint

Interferons
Glucocorticoids
Acquired Immunodeficiency Syndrome
Hydrocortisone
Monocytes
Adrenocorticotropic Hormone
Poly I
Interferon Receptors
Poly C
Plasmas
Mifepristone
Glucocorticoid Receptors
Poly I-C
Dexamethasone
Cytokines

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Glucocorticoids and interferon-α in the acquired immunodeficiency syndrome. / Norbiato, Guido; Bevilacqua, Maurizio; Vago, Tarcisio; Clerici, Mario.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 81, No. 7, 1996, p. 2601-2606.

Research output: Contribution to journalArticle

Norbiato, Guido ; Bevilacqua, Maurizio ; Vago, Tarcisio ; Clerici, Mario. / Glucocorticoids and interferon-α in the acquired immunodeficiency syndrome. In: Journal of Clinical Endocrinology and Metabolism. 1996 ; Vol. 81, No. 7. pp. 2601-2606.
@article{e5d36ff9384a4f27ac5a9ad6fe9dd6ae,
title = "Glucocorticoids and interferon-α in the acquired immunodeficiency syndrome",
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.",
author = "Guido Norbiato and Maurizio Bevilacqua and Tarcisio Vago and Mario Clerici",
year = "1996",
doi = "10.1210/jc.81.7.2601",
language = "English",
volume = "81",
pages = "2601--2606",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "The Endocrine Society",
number = "7",

}

TY - JOUR

T1 - Glucocorticoids and interferon-α in the acquired immunodeficiency syndrome

AU - Norbiato, Guido

AU - Bevilacqua, Maurizio

AU - Vago, Tarcisio

AU - Clerici, Mario

PY - 1996

Y1 - 1996

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0029978513&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029978513&partnerID=8YFLogxK

U2 - 10.1210/jc.81.7.2601

DO - 10.1210/jc.81.7.2601

M3 - Article

C2 - 8675584

AN - SCOPUS:0029978513

VL - 81

SP - 2601

EP - 2606

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 7

ER -