Cortisol resistance in acquired immunodeficiency syndrome

Area of Science:

• Endocrinology
• Immunology
• Virology

Background:

• Acquired immunodeficiency syndrome (AIDS) can manifest with hypercortisolism.
• Some AIDS patients present with an Addisonian picture, suggesting potential endocrine dysfunction.
• Peripheral resistance to glucocorticoids is a suspected complication in these patients.

Purpose of the Study:

• To investigate glucocorticoid receptor characteristics in AIDS patients with hypercortisolism and an Addisonian picture.
• To determine if abnormal glucocorticoid receptors contribute to peripheral resistance in these patients.
• To explore the functional consequences of these receptor abnormalities on immune cell activity.

Main Methods:

• Assessed glucocorticoid receptor density and affinity using [3H]dexamethasone binding on mononuclear leukocytes.
• Measured the effect of dexamethasone on [3H]thymidine incorporation to assess receptor activation.
• Compared receptor characteristics between AIDS patients with and without an Addisonian picture, and with healthy controls.

Main Results:

• AIDS patients with an Addisonian picture showed significantly increased glucocorticoid receptor density compared to controls and AIDS patients without this picture.
• Glucocorticoid receptor affinity (Kd) was markedly decreased in AIDS patients with an Addisonian picture.
• [3H]Thymidine incorporation response to dexamethasone was blunted in these patients, indicating impaired receptor activation.

Conclusions:

• AIDS patients with hypercortisolism and Addisonian features have abnormal glucocorticoid receptors on lymphocytes.
• These receptor abnormalities are associated with peripheral resistance to glucocorticoids.
• Glucocorticoid resistance may play a role in the complex immune-endocrine dysregulation observed in AIDS.