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 language | English |
|---|---|
| Pages (from-to) | 2601-2606 |
| Number of pages | 6 |
| Journal | Journal of Clinical Endocrinology and Metabolism |
| Volume | 81 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - 1996 |
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ASJC Scopus subject areas
- Biochemistry
- Endocrinology, Diabetes and Metabolism
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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 journal › Article
}
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 -