TNF‐α–secreting monocytes are recruited into the brain of cholestatic mice†‡
Bibliographic record
Abstract
Signaling occurs between the liver and brain in cholestatic liver disease, giving rise to sickness behaviors such as fatigue. However, the signaling pathways involved are poorly defined. Circulating inflammatory mediator levels are increased in cholestasis, leading to speculation that they may be capable of activating circulating immune cells that subsequently could gain access to the brain. Indeed, we have identified that at day 10 after bile duct resection-induced cholestasis, there is activation of circulating monocytes that express tumor necrosis factor alpha (TNF-alpha) in conjunction with increased expression of adhesion molecules by cerebral endothelium. Moreover, using intravital microscopy, we have identified markedly enhanced leukocytes rolling along cerebral endothelial cells, mediated by P-selectin, in bile duct-resected (BDR) but not control mice. In addition, we have identified increased infiltration of monocytes (but not lymphocytes) into the brains of BDR mice and found that these infiltrating monocytes produce TNF-alpha. Furthermore, infiltration of TNF-alpha-secreting monocytes into the brains of cholestatic mice is associated with a broad activation of resident brain macrophages to produce TNF-alpha. In conclusion, cholestasis is associated with an activation of cerebral endothelium that recruits TNF-alpha-producing monocytes into the brain. We hypothesize that enhanced TNF-alpha release within the brain may contribute to the development of cholestasis-associated sickness behaviors, including fatigue.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 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".