Glucocorticoids and interferon-alpha in the acquired immunodeficiency syndrome
| Autor: | Maurizio Bevilacqua, Tarcisio Vago, Mario Clerici, G. Norbiato |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
Adult
Male medicine.medical_specialty Hydrocortisone medicine.drug_class medicine.medical_treatment Endocrinology Diabetes and Metabolism Clinical Biochemistry Drug Resistance Alpha interferon Biology Tritium Peripheral blood mononuclear cell Biochemistry Dexamethasone Monocytes Glucocorticoid receptor Receptors Glucocorticoid Endocrinology Adrenocorticotropic Hormone Acquired immunodeficiency syndrome (AIDS) Internal medicine Interferon α Humans Medicine Receptor Glucocorticoids Triglycerides Acquired Immunodeficiency Syndrome business.industry Biochemistry (medical) Interferon-alpha Middle Aged Receptor antagonist medicine.disease Cytokine Immunology Female business hormones hormone substitutes and hormone antagonists medicine.drug |
| Zdroj: | Journal of Clinical Endocrinology & Metabolism. 81:2601-2606 |
| ISSN: | 0021-972X |
| DOI: | 10.1210/jc.81.7.2601 |
| Popis: | Some patients with acquired immunodeficiency syndrome (AIDS) develop glucocorticoid resistance characterized by low receptor affinity (Kd) for glucocorticoids in mononuclear, cells and high values of ACTH and cortisol. As glucocorticoids regulate interferon-alpha (IFN alpha) production, we hypothesized that IFN alpha, a cytokine produced predominantly by monocytes in AIDS, should be increased in cortisol-resistant AIDS, attributing the lack of cortisol inhibition to IFN alpha production. Therefore, we examined glucocorticoid receptor characteristics on monocytes by [3H]dexamethasone binding and measured IFN alpha, 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 Kd 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). IFN alpha 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 IFN alpha and receptor Kd on monocytes of AIDS-GR (r = 0.77) and between IFN alpha and plasma cortisol in the same group (r = 0.74). The poly(I)-poly(C)-induced IFN alpha production by monocytes was inhibited by glucocorticoids in the C and AIDS-C groups (approximately 80% inhibition in both groups); the effect was reversed by the receptor antagonist RU-38486. By contrast, glucocorticoids failed to inhibit IFNalpha production from AIDS-GR monocytes (approximately 20% inhibition). In conclusion, elevated IFN alpha levels in AIDS-GR may be due to the lack of inhibitory effect of cortisol on IFN alpha production due to cortisol resistance in monocytes. |
| Databáze: | OpenAIRE |
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