ArticleNature immunology2014
Signaling by IL-6 promotes alternative activation of macrophages to limit endotoxemia and obesity-associated resistance to insulin.
Article in Nature immunology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 407 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
407 citing papers in PubMed, 1 synthesis or guideline pooled it, 723 citations in OpenAlex.
- Meta-analysis: Interleukin 6 gene -174G/C polymorphism associated with type 2 diabetes mellitus and interleukin 6 changes.Journal of cellular and molecular medicine · 2021Pooled it
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- Concurrent Aerobic and Strength Training with Caloric Restriction Reduces Insulin Resistance in Obese Premenopausal Women: A Randomized Controlled Trial.Medicina (Kaunas, Lithuania) · 2023Trial
- Changes in Circulating Cytokines and Adipokines After RYGB in Patients with and without Type 2 Diabetes.Obesity (Silver Spring, Md.) · 2021Trial
- Early postnatal antibiotic-associated gut microbiota alterations might promote long-term lipid metabolism via brown adipose tissue metabolic programming.Gut microbes · 2026Article
- Coenzyme A activates TLR4 and enhances alternative macrophage activation in line with MyD88 agonism.EMBO reports · 2026Article
- Cyclooxygenase-mediated IL-10Rα signaling underlies pro-tumor phenotypes of macrophages in glioma.Cell death & disease · 2026Article
- Integrated multi-omics profiling of gut bacterial extracellular vesicles links cargo composition to host transcriptional responses.bioRxiv : the preprint server for biology · 2026Article
- Cell-type-specific proximity labeling of organ secretomes reveals energy balance-dependent proteomic remodeling.Cell reports · 2026Article
- Leukocytic ADAM10 and ADAM17 modulate disease severity and systemic outcome in bacterial and viral pneumonia.The European respiratory journal · 2026Article
- Review
- Advances in Adipose Tissue Biology.Endocrine reviews · 2026Review
- Combined antagonism of Oncostatin M (OSM) and Interleukin 6 (IL-6) provides both anti-fibrotic and anti-inflammatory benefit in pulmonary fibrosis.bioRxiv : the preprint server for biology · 2026Article
- Cell type-specific proximity labeling of organ secretomes reveals energy balance-dependent proteomic remodeling.bioRxiv : the preprint server for biology · 2026Article
- The hidden cost of antibiotics: microbial dysbiosis-induced SCFA imbalance and its underlying mechanisms.Frontiers in immunology · 2026Review
- A transcriptomic atlas of macrophage polarization induced by inflammatory and reparative cytokines reveals cytokine-specific and synergistic polarization programs.Frontiers in immunology · 2026Article
- Preventing Metabolic Syndrome in Adolescents Through Exercise.Advances in experimental medicine and biology · 2026Review
- Neutrophil-macrophage crosstalk network in acute lung injury: feedback circuits linking cytokine storm and cell death.Frontiers in cellular and infection microbiology · 2026Review
- Prevotella copri promotes white adipose browning and ameliorates adiposity.Nature communications · 2025Article
- HDL-C and systemic inflammatory response index mediate the association between visceral adipose tissue and risk of cardiovascular disease among young and middle-aged adults with prediabetes or diabetes: a national cohort study.Journal of translational medicine · 2025Article
347 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 6 institutions in 3 countries.
Funding
Abstract
Obesity and resistance to insulin are closely associated with the development of low-grade inflammation. Interleukin 6 (IL-6) is linked to obesity-associated inflammation; however, its role in this context remains controversial. Here we found that mice with an inactivated gene encoding the IL-6Rα chain of the receptor for IL-6 in myeloid cells (Il6ra(Δmyel) mice) developed exaggerated deterioration of glucose homeostasis during diet-induced obesity, due to enhanced resistance to insulin. Tissues targeted by insulin showed increased inflammation and a shift in macrophage polarization. IL-6 induced expression of the receptor for IL-4 and augmented the response to IL-4 in macrophages in a cell-autonomous manner. Il6ra(Δmyel) mice were resistant to IL-4-mediated alternative polarization of macrophages and exhibited enhanced susceptibility to lipopolysaccharide (LPS)-induced endotoxemia. Our results identify signaling via IL-6 as an important determinant of the alternative activation of macrophages and assign an unexpected homeostatic role to IL-6 in limiting inflammation.
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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.