Glucocorticoid resistance and the immune function in the immunodeficiency syndrome

Guido Norbiato, Maurizio Bevilacqua, Tarcisio Vago, Mario Clerici

Research output: Contribution to journalArticlepeer-review

Abstract

Glucocorticoids, the final product of HPA axis, and their receptors (GRs) on mononuclear cells are crucial mediators in the endocrine-immune interaction. An alteration in GRs involving a lower receptor affinity (K(d)) for glucocorticoids has been found in a group of advanced AIDS patients, who developed Addisonian symptoms (weakness, weight loss, hypotension, hyponatremia, and intense mucocutaneous melanosis) in spite of hypercortisolism and normal or slightly elevated values of ACTH (AIDS-GR). In these patients, data for the suppression test showed decreased cortisol and ACTH suppression in response to exogenous dexamethasone. The inhibitory effect of dexamethasone on radiolabeled-thymidine incorporation in mononuclear cells from these patients was also reduced. Monocytes of AIDS-GR patients had a receptor K(d) of 10.5 ± 4.2 nmol/l that was higher than that of other AIDS patients (AIDS-C) (2.9 ± 0.8 nmol/l) and normal subjects (2.0 ± 0.8 nmol/l: p <0.01). Correlations were found between plasmatic IFN-alpha and receptor K(d) on monocytes of AIDS-GR (γ = 0.77). Poly (i)-poly (c)-induced IFN-alpha production by monocytes was inhibited by glucocorticoids in the AIDS-C group and controls (approx. 80% in both groups): The effect was reversed by the receptor antagonist RU-486. By contrast, glucocorticoid did not inhibit IFN-alpha production in AIDS-GR group. In conclusion, levels of plasmatic IFN-alpha, a cytokine with antiviral properties, may be increased several times, and dexamethasone fails to inhibit monocytes IFN-alpha production only in AIDS with cortisol resistance, a disturbance that confirms an important immunoregulatory role of glucocorticoids in HIV disease.

Original languageEnglish
Pages (from-to)835-847
Number of pages13
JournalAnnals of the New York Academy of Sciences
Volume840
DOIs
Publication statusPublished - May 1 1998

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint Dive into the research topics of 'Glucocorticoid resistance and the immune function in the immunodeficiency syndrome'. Together they form a unique fingerprint.

Cite this