ArticleProceedings of the National Academy of Sciences of the United States of America2015
Extracellular forms of IL-37 inhibit innate inflammation in vitro and in vivo but require the IL-1 family decoy receptor IL-1R8.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 125 papers.
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Who cites it
125 citing papers in PubMed, 228 citations in OpenAlex.
- Effect of vitamin D supplementation on inflammatory status and behavioral symptoms in children with autism spectrum disorders: a double-blind randomized clinical trial.BMC pediatrics · 2025Trial
- Article
- IL-37/IL-1R8 axis: a novel major mechanism of control at the interface between tumor and immune cells.Oncoimmunology · 2026Review
- Research progress on the role of IL‑37 in gynecological and obstetrics‑related diseases (Review).International journal of molecular medicine · 2026Review
- Interleukin-37 in Cancer Angiogenesis: Mechanisms, Therapeutic Potential, and Future Perspectives.Cancer reports (Hoboken, N.J.) · 2026Review
- Pathogenesis of bronchopulmonary dysplasia: an immunological perspective.Frontiers in immunology · 2026Review
- IL-37 and IL-38 in sepsis: immune-metabolic rheostats in a dynamic inflammatory continuum.Frontiers in immunology · 2026Review
- The complex role of IL-37 in cancer pathogenesis: exploring its influence on hallmarks of cancer.Frontiers in immunology · 2026Review
- Programmed Probiotics Generate Interleukin-37b-Bearing Nanovesicles In Situ for Precision Immunomodulation in Colitis.Research (Washington, D.C.) · 2026Article
- IL-1 family cytokines in inflammation and immunity.Cellular & molecular immunology · 2025Review
- Beyond Negative Regulation: IL-1R8 and IL-1R2 as Novel Immune Checkpoints.European journal of immunology · 2025Review
- High-dose IL-37 promotes inflammatory activity of macrophage via Preferential ligation of the IL-18Rα.Scientific reports · 2025Article
- Interleukin-37 modulates microglial phenotype and inhibits inflammatory response via the MyD88/NF-κB pathway in lipopolysaccharide-induced neuroinflammation.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Article
- Interleukin-37 Suppresses the Function of Type 2 Follicular Helper T in Allergic Rhinitis.Biomedicines · 2025Article
- Interleukin-37 in respiratory diseases: molecular mechanisms and immune modulation.Frontiers in immunology · 2025Review
- Micro- and nano-plastics induce inflammation and cell death in human cells.Frontiers in immunology · 2025Article
- Recombinant expression, downstream optimization, and therapeutic evaluation of recombinant human interleukin-37 for cancer therapy.Biotechnology letters · 2024Article
- IL-37 Isoform A Prevents Collagen-Induced Arthritis in Mice by Modulating the Th17/Treg Balance via IL1R8 Receptors.International journal of molecular sciences · 2024Article
- The effect and mechanism of IL-37d on neutrophil recruitment in the early stage of tumor metastasis in the lungs.Discover oncology · 2024Article
- Circulating Interleukins-33 and -37 and Their Associations with Metabolic Syndrome in Arab Adults.International journal of molecular sciences · 2024Article
65 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 4 institutions in 4 countries.
Funding
Abstract
Similar to IL-1α and IL-33, IL-1 family member IL-37b translocates to the nucleus and is associated with suppression of innate and adaptive immunity. Here we demonstrate an extracellular function of the IL-37 precursor and a processed form. Recombinant IL-37 precursor reduced LPS-induced IL-6 by 50% (P < 0.001) in highly inflammatory human blood-derived M1 differentiated macrophages derived from selective subjects but not M2 macrophages. In contrast, a neutralizing monoclonal anti-IL-37 increased LPS-induced IL-6, TNFα and IL-1β (P < 0.01). The suppression by IL-37 was consistently observed at low picomolar but not nanomolar concentrations. Whereas LPS induced a 12-fold increase in TNFα mRNA, IL-37 pretreatment decreased the expression to only 3-fold over background (P < 0.01). Mechanistically, LPS-induced p38 and pERK were reduced by IL-37. Recombinant IL-37 bound to the immobilized ligand binding α-chain of the IL-18 receptor as well as to the decoy receptor IL-1R8. In M1 macrophages, LPS increased the surface expression of IL-1R8. Compared with human blood monocytes, resting M1 cells express more surface IL-1R8 as well as total IL-1R8; there was a 16-fold increase in IL-1R8 mRNA levels when pretreated with IL-37. IL-37 reduced LPS-induced TNFα and IL-6 by 50-55% in mouse bone marrow-derived dendritic cells, but not in dendritic cells derived from IL-1R8-deficient mice. In mice subjected to systemic LPS-induced inflammation, pretreatment with IL-37 reduced circulating and organ cytokine levels. Thus, in addition to a nuclear function, IL-37 acts as an extracellular cytokine by binding to the IL-18 receptor but using the IL-1R8 for its anti-inflammatory properties.
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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.