Effects of endogenous glucocorticoid secretion on the interleukin-6 response to bacterial endotoxin in pregnant and non-pregnant rats
Bibliographic record
Abstract
Glucocorticoids (GCs) are released in response to immune activation by the bacterial endotoxin, lipopolysaccharide (LPS). However, GC secretion in response to immune activation and other stressors is attenuated at term of pregnancy. GCs are important modulators of the immune response, and both pro- and anti-inflammatory effects are described. Here, we examined whether GC secretion in response to LPS is maintained in earlier pregnancy before term, and investigated the role of endogenous GCs in modulating LPS-induced circulating cytokines, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), in pregnant compared to non-pregnant female rats. Plasma corticosterone (Cort) and ACTH responses to LPS were well maintained in pregnant rats at embryonic days 15/16 (E15/16) and E18/19 compared to non-pregnant rats. At E19, maternal LPS administration increased fetal plasma Cort and decreased testosterone in male fetuses. In non-pregnant animals, pretreatment with the GC synthesis inhibitor, metyrapone, inhibited the LPS-induced increase in IL-6, and the IL-6 response was restored by Cort replacement, indicating that LPS induction of IL-6 is Cort-dependent. In E15 pregnant animals, metyrapone had no effect on LPS-induced IL-6 levels, indicating that LPS-induction of IL-6 is not dependent on Cort. These contrasting patterns of IL-6 induction in non-pregnant and pregnant animals were reflected in levels of hypothalamic Socs3 mRNA, an indicator of IL-6 signaling pathway activation. In both non-pregnant and pregnant rats, LPS-induced plasma TNF-α responses were inhibited by metyrapone but not re-instated by Cort replacement. It is suggested that altered GC regulation of IL-6 may be required to sustain specialized functions of IL-6 during pregnancy.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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 teacher head, 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".