ArticleeLife2024
Leucine alleviates cytokine storm syndrome by regulating macrophage polarization via the mTORC1/LXRα signaling pathway.
Article in eLife, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 23 citations in OpenAlex.
- Review
- Clostridium butyricum and its metabolites regulate macrophage polarization through miR-146a to antagonize gouty arthritis.Journal of advanced research · 2026Article
- Amino acid metabolism modulates macrophage polarization: implications for autoimmune-related diseases.Frontiers in immunology · 2026Review
- Rus-GXF, a ruscogenin glycoside, binds to the ADP-binding domain of JAK1 to prevent inflammation and barrier damage in acute lung injury.Frontiers in pharmacology · 2026Article
- Review
- Branched-chain amino acids and sepsis: from pathological mechanisms to clinical interventions.Nutrition & metabolism · 2025Review
- Leucine Attenuates Osteoarthritis via mTORC1/LXRα-Mediated Macrophage Reprogramming and Rspo2/β-Catenin Axis Suppression.Cartilage · 2025Article
- Angiopoietin-like protein 8 orchestrates macrophage glycogen metabolism and polarization via the JNK signaling pathway in cytokine storm syndrome.Cell & bioscience · 2025Article
- mTOR Signaling in Macrophages: All Depends on the Context.International journal of molecular sciences · 2025Review
- Metabolic Changes in Zebrafish Larvae Infected withMetabolites · 2025Article
- Roles of circadian clocks in macrophage metabolism: implications in inflammation and metabolism of lipids, glucose, and amino acids.American journal of physiology. Endocrinology and metabolism · 2025Review
- Reprogramming Macrophage Phenotypes With Photobiomodulation for Improved Inflammation Control in ENT Organ Tissues.Clinical and experimental otorhinolaryngology · 2025Article
- Integrated analysis of stem cell-related genes shared between type 2 diabetes mellitus and sepsis.Frontiers in chemistry · 2025Article
- Regulation of dendritic cell biology by amino acids and their transporters.Frontiers in immunology · 2025Review
- Interacting roles of gut microbiota and T cells in the development of autoimmune hepatitis.Frontiers in immunology · 2025Review
- Crosstalk between macrophages and immunometabolism and their potential roles in tissue repair and regeneration.Heliyon · 2024Review
- Delayed macrophage targeting by clodronate liposomes worsens the progression of cytokine storm syndrome.Frontiers in immunology · 2024Article
- Attenuating mitochondrial dysfunction-derived reactive oxygen species and reducing inflammation: the potential of Daphnetin in the viral pneumonia crisis.Frontiers in pharmacology · 2024Review
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
Cytokine storms are associated with severe pathological damage and death in some diseases. Excessive activation of M1 macrophages and the subsequent secretion of pro-inflammatory cytokines are a major cause of cytokine storms. Therefore, promoting the polarization of M2 macrophages to restore immune balance is a promising therapeutic strategy for treating cytokine storm syndrome (CSS). This study was aimed at investigating the potential protective effects of leucine on lipopolysaccharide (LPS)-induced CSS in mice and exploring the underlying mechanisms. CSS was induced by LPS administration in mice, which were concurrently administered leucine orally. In vitro, bone marrow derived macrophages (BMDMs) were polarized to M1 and M2 phenotypes with LPS and interleukin-4 (IL-4), respectively, and treated with leucine. Leucine decreased mortality in mice treated with lethal doses of LPS. Specifically, leucine decreased M1 polarization and promoted M2 polarization, thus diminishing pro-inflammatory cytokine levels and ameliorating CSS in mice. Further studies revealed that leucine-induced macrophage polarization through the mechanistic target of rapamycin complex 1 (mTORC1)/liver X receptor α (LXRα) pathway, which synergistically enhanced the expression of the IL-4-induced M2 marker Arg1 and subsequent M2 polarization. In summary, this study revealed that leucine ameliorates CSS in LPS mice by promoting M2 polarization through the mTORC1/LXRα/Arg1 signaling pathway. Our findings indicate that a fundamental link between metabolism and immunity contributes to the resolution of inflammation and the repair of damaged tissues.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.