Transforming growth factor-β1 blocks in vitro cardiac myocyte depression induced by tumor necrosis factor-α, interleukin-1β, and human septic shock serum
Bibliographic record
Abstract
OBJECTIVE: Serum from patients with septic shock induces depression of myocyte contractility in vitro that is proportional the reduction of ejection fraction in vivo. This effect is mediated, in part, by tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta. Transforming growth factor (TGF)-beta is an immunomodulatory cytokine with a broad range of anti-inflammatory effects. Using an in vitro assay, this study sought to determine the effect of TGF-beta1 on myocyte depression induced by TNF-alpha, IL-1beta, and serum with known depressant activity from patients with septic shock. DESIGN: The maximum extent of shortening of electrically paced rat cardiac myocytes in tissue culture was quantified by a closed-loop video tracking system. Myocytes were exposed to different combinations of TNF-alpha, IL-1beta, septic serum, and TGF-beta1. SETTING: Basic research laboratory. MEASUREMENTS AND MAIN RESULTS: Increasing concentrations of TNF-alpha and IL-1beta each caused significant depression of maximum extent of myocyte shortening in vitro over 30 mins (p<.0001). Similarly, a synergistic combination of TNF-alpha and IL-1beta as well as serum with known depressant activity from five patients with acute septic shock induced significant depression of cardiac myocyte contraction (p<.01). Increasing concentrations of TGF-beta1 alone had no effect on maximum extent of cardiac myocyte contraction. However, myocytes that were co-incubated with increasing concentrations of TGF-beta1 demonstrated dose-dependent reversal of depression induced by TNF-alpha or IL-1beta (p<.0001). Similarly, depressant effects caused by synergistic concentrations of TNF-alpha and IL-1beta and serum from all five patients with septic shock were prevented by co-incubation with TGF-beta1. CONCLUSIONS: These data demonstrate that depression of in vitro cardiac myocyte contraction induced by proinflammatory cytokines and septic serum can be blocked by TGF-beta1. TGF-beta1 may have potential as therapy for sepsis-associated myocardial depression in humans.
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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) | 0.001 | 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 | 0.001 |
| 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".