The Dual Role of Hypoxia-Inducible Factor-1α in Sepsis-Induced Immunomodulation and Organ Dysfunction: A Systematic Review and Meta-Analysis
Notice bibliographique
Résumé
Background: Sepsis, a life-threatening organ dysfunction caused by a dysregulated host response to infection, remains a leading cause of global mortality. Hypoxia-inducible factor-1α (HIF-1α) is a master transcriptional regulator of the cellular adaptive response to hypoxia but plays a complex, paradoxical role in sepsis. While essential for innate immune function, its sustained activation may amplify inflammation and drive organ damage. This meta-analysis was conducted to synthesize the evidence on the association of HIF-1α with key markers of immunomodulation and organ dysfunction in sepsis. Methods: We performed a systematic review and meta-analysis following PRISMA guidelines. A comprehensive search of PubMed, Scopus, and Web of Science was conducted for studies published between January 2014 and December 2024. We included observational studies that measured HIF-1α levels in adult sepsis patients and reported outcomes related to organ dysfunction (Sequential Organ Failure Assessment [SOFA] score) or mortality, and immunomodulation (Interleukin-6 [IL-6] levels). Seven studies meeting the inclusion criteria were included in the final analysis. Data were pooled using a random-effects model. Standardized Mean Difference (SMD) and Odds Ratios (OR) with 95% confidence intervals (CI) were calculated. Results: The seven included studies comprised 1,288 patients. The overall quality of the included studies was moderate to high as per the Newcastle-Ottawa Scale. The pooled analysis revealed that HIF-1α levels were significantly elevated in sepsis patients who died compared to those who survived (OR = 2.68, 95% CI: 1.55–4.64, p < 0.001), with moderate heterogeneity (I² = 45%). Furthermore, HIF-1α levels were strongly associated with greater organ dysfunction, as measured by the SOFA score (5 studies; SMD = 0.92, 95% CI: 0.51–1.33, p < 0.0001), with substantial heterogeneity (I² = 78%). HIF-1α levels also showed a significant positive correlation with the pro-inflammatory cytokine IL-6 (4 studies; SMD = 1.15, 95% CI: 0.65–1.65, p < 0.00001), with high heterogeneity (I² = 82%). Conclusion: This meta-analysis provides robust evidence that elevated HIF-1α levels are significantly associated with increased sepsis severity, characterized by greater organ dysfunction, a heightened pro-inflammatory state, and a higher risk of mortality. These findings underscore the maladaptive consequences of sustained HIF-1α activation in sepsis, positioning it as a critical prognostic biomarker and a complex, high-value target for future therapeutic modulation.
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,008 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,005 | 0,001 |
| Bibliométrie | 0,003 | 0,004 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».