Fever integrates antimicrobial defences, inflammation control, and tissue repair in a cold-blooded vertebrate
Bibliographic record
Abstract
Multiple lines of evidence support the value of moderate fever to host survival, but the mechanisms involved remain unclear. This is difficult to establish in warm-blooded animal models, given the strict programmes controlling core body temperature and the physiological stress that results from their disruption. Thus, we took advantage of a cold-blooded teleost fish that offered natural kinetics for the induction and regulation of fever and a broad range of tolerated temperatures. A custom swim chamber, coupled to high-fidelity quantitative positional tracking, showed remarkable consistency in fish behaviours and defined the febrile window. Animals exerting fever engaged pyrogenic cytokine gene programmes in the central nervous system, increased efficiency of leukocyte recruitment into the immune challenge site, and markedly improved pathogen clearance in vivo, even when an infecting bacterium grew better at higher temperatures. Contrary to earlier speculations for global upregulation of immunity, we identified selectivity in the protective immune mechanisms activated through fever. Fever then inhibited inflammation and markedly improved wound repair. Artificial mechanical hyperthermia, often used as a model of fever, recapitulated some but not all benefits achieved through natural host-driven dynamic thermoregulation. Together, our results define fever as an integrative host response that regulates induction and resolution of acute inflammation, and demonstrate that this integrative strategy emerged prior to endothermy during evolution.
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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".