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Record W3155096718 · doi:10.1096/fj.202100388r

Interleukin‐6 blockade, a potential adjunct therapy for post‐burn hypermetabolism

2021· article· en· W3155096718 on OpenAlexafffund
Dalia Barayan, Abdikarim Abdullahi, Roohi Vinaik, Carly M. Knuth, Christopher Auger, Marc G. Jeschke

Bibliographic record

VenueThe FASEB Journal · 2021
Typearticle
Languageen
FieldMedicine
TopicBurn Injury Management and Outcomes
Canadian institutionsHealth Sciences CentreSunnybrook Health Science CentreUniversity of TorontoSunnybrook Hospital
FundersNational Institute of General Medical SciencesCanadian Institutes of Health ResearchNational Institute on AgingNational Institutes of HealthCanada Foundation for Innovation
KeywordsHypermetabolismMedicineCachexiaAdverse effectSteatosisInternal medicineBlockadeLipotoxicityFibrosisBurn injuryWeight lossOrgan dysfunctionEndocrinologyGastroenterologySurgeryObesitySepsisInsulin resistance

Abstract

fetched live from OpenAlex

Severe burns remain a leading cause of death and disability worldwide. Despite advances in patient care, the excessive and uncontrolled hypermetabolic stress response induced by this trauma inevitably affects every organ system causing substantial morbidity and mortality. Recent evidence suggests interleukin-6 (IL-6) is a major culprit underlying post-burn hypermetabolism. Indeed, genetic deletion of IL-6 alleviates various complications associated with poor clinical outcomes including the adverse remodeling of adipose tissue, cachexia and hepatic steatosis. Thus, pharmacological blockade of IL-6 may be a more favorable treatment option to fully restore metabolic function after injury. To test this, we investigated the safety and effectiveness of blocking IL-6 for post-burn hypermetabolism using a validated anti-IL-6 monoclonal antibody (mAb) in our experimental murine model. Here, we show daily anti-IL-6 mAb administration protects against burn-induced weight loss (P < .0001) without any adverse effect on mortality. At the organ level, post-burn treatment with the IL-6 blocker suppressed the thermogenic activation of adipose tissue (P < .01) and its associated wasting (P < .05). The reduction of browning-induced lipolysis (P < .0001) indirectly decreased hepatic lipotoxicity (P < .01) which improved liver dysfunction (P < .05). Importantly, the beneficial effects of this anti-IL-6 agent extended to the skin, reflected by the decrease in excessive collagen deposition (P < .001) and genes involved in pathologic fibrosis and scarring (P < .05). Together, our results indicate that post-burn IL-6 blockade leads to significant improvements in systemic hypermetabolism by inhibiting pathological alterations in key immunometabolic organs. These findings support the therapeutic potential of anti-IL-6 interventions to improve care, quality of life, and survival in burned patients.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesInsufficient payload (model declined to judge)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.348
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

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.

Opus teacher head0.020
GPT teacher head0.274
Teacher spread0.255 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designBench or experimental
Domainnot available
GenreEmpirical

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".

Quick stats

Citations23
Published2021
Admission routes2
Has abstractyes

Explore more

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