Impaired glucocorticoid receptor function evolves in aberrant physiological responses to bacterial endotoxin

Area of Science:

• Neuroendocrinology
• Immunology
• Genetics

Background:

• Glucocorticoid receptor (GR) plays a crucial role in regulating physiological and immune responses.
• Dysfunction of GR can lead to altered responses to inflammatory challenges.
• Understanding these alterations is vital for comprehending stress-related disorders.

Purpose of the Study:

• To investigate the consequences of impaired glucocorticoid receptor (GR) function on neuroimmunoendocrine responses to an inflammatory challenge.
• To analyze the physiological and humoral changes in transgenic mice with GR dysfunction.

Main Methods:

• Utilized transgenic mice with impaired glucocorticoid receptor (GR-i mice) expressing antisense RNA against GR.
• Monitored body temperature and locomotion using intraperitoneal biotelemetry transmitters.
• Administered endotoxin to induce an inflammatory challenge and analyzed plasma ACTH, corticosterone, and serum cytokine levels (IL-1β, IL-6, TNF-α).

Main Results:

• GR-i mice exhibited altered body temperature regulation and locomotion compared to controls.
• Endotoxin challenge in GR-i mice resulted in a delayed and prolonged fever response.
• GR-i mice showed augmented ACTH release and significantly elevated TNF-α levels post-endotoxin, while IL-1β and IL-6 levels were comparable to controls.

Conclusions:

• Life-long impairment of the glucocorticoid receptor (GR) leads to aberrant physiological and humoral responses to acute inflammatory challenges.
• These findings enhance the understanding of neuroendocrine and physiological disturbances associated with stress-related disorders.
• The study underscores the critical role of GR in mediating adaptive responses to inflammation and stress.