Differential susceptibility to lethal endotoxaemia in mice deficient in IL‐1α, IL‐1β or IL‐1 receptor type I
Why this work is in the frame
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Bibliographic record
Abstract
The role of intereukin-1 (IL-1) in mortality caused by endotoxaemia remains controversial. While IL-1 receptor antagonist (IL-1Ra) protects mice from lethal endotoxaemia, mice deficient in IL-1β (IL-1β⁻( /)⁻) display normal susceptibility to lipopolysaccharide (LPS). The aim of this study was to identify the source of these discrepancies. Mice deficient in IL-1α, IL-1β or IL-1R type I were injected intraperitoneally with Escherichia coli or Salmonella typhimurium LPS. Survival of the mice was examined and compared with C57/Bl6 wild-type mice. In addition, serum cytokine concentrations were determined after LPS challenge and in vitro cytokine production by peritoneal macrophages was analysed. Clearance of radioactive IL-1α was examined in IL-1α⁻(/)⁻ and wild-type mice. IL-1β⁻(/)⁻ mice were normally susceptible to endotoxaemia and cytokine production did not differ from that in control mice. Surprisingly, LPS mortality in IL-1α⁻(/)⁻ mice was significantly greater than that in control mice, accompanied by higher interferon-γ release. These effects were mediated by a distorted homeostasis of IL-1RI receptors, as shown by a strongly delayed clearance of IL-1α. In contrast to the IL-1α⁻(/)⁻ and IL-1β⁻(/)⁻ mice, IL-1RI⁻(/)⁻ mice were completely resistant to high doses of LPS. In conclusion, IL-1RI-mediated signals are crucial in mediating mortality occurring as a result of lethal endotoxaemia. Investigation of IL-1-mediated pathways in IL-1 knock-out mice is complicated by a distorted homeostasis of IL-1Rs.
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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 | 0.001 |
| 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 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 it