The HPA – Immune Axis and the Immunomodulatory Actions of Glucocorticoids in the Brain
Bibliographic record
Abstract
In response to physiological and psychogenic stressors, the hypothalamic-pituitary-adrenal (HPA) axis orchestrates the systemic release of glucocorticoids (GCs). By virtue of nearly ubiquitous expression of the GC receptor and the multifaceted metabolic, cardiovascular, cognitive, and immunologic functions of GCs, this system plays an essential role in the response to stress and restoration of an homeostatic state. GCs act on almost all types of immune cells and were long recognized to perform salient immunosuppressive and anti-inflammatory functions through various genomic and non-genomic mechanisms. These renowned effects of the steroid hormone have been exploited in the clinic for the past 70 years and synthetic GC derivatives are commonly used for the therapy of various allergic, autoimmune, inflammatory, and hematological disorders. The role of the HPA axis and GCs in restraining immune responses across the organism is however still debated in light of accumulating evidence suggesting that GCs can also have both permissive and stimulatory effects on the immune system under specific conditions. Such paradoxical actions of GCs are particularly evident in the brain, where substantial data support either a beneficial or detrimental role of the steroid hormone. In this review, we examine the roles of GCs on the innate immune system with a particular focus on the CNS compartment. We also dissect the numerous molecular mechanisms through which GCs exert their effects and discuss the various parameters influencing the paradoxical immunomodulatory functions of GCs in the brain.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.002 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".