ArticleProceedings of the National Academy of Sciences of the United States of America2012
IL-38 binds to the IL-36 receptor and has biological effects on immune cells similar to IL-36 receptor antagonist.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 185 papers, 3 of them syntheses that pooled it.
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Who cites it
185 citing papers in PubMed, 3 syntheses or guidelines pooled it, 373 citations in OpenAlex.
- Immunobiological Properties and Clinical Applications of Interleukin-38 for Immune-Mediated Disorders: A Systematic Review Study.International journal of molecular sciences · 2021Pooled it
- Cytokine Pathways and Investigational Target Therapies in Hidradenitis Suppurativa.International journal of molecular sciences · 2020Pooled it
- Trans-ethnic meta-analysis of white blood cell phenotypes.Human molecular genetics · 2014Pooled it
- IL-36γ is a pivotal inflammatory player in periodontitis-associated bone loss.Scientific reports · 2019Trial
- Differential Expression of IL-36 Family Members and IL-38 by Immune and Nonimmune Cells in Patients with Active Inflammatory Bowel Disease.BioMed research international · 2018Trial
- Cytokine multimerization: when more is more and sometimes less.Nature reviews. Immunology · 2026Review
- Advances in targeting IL-1 family cytokines for the treatment of inflammatory diseases.Nature reviews. Rheumatology · 2026Review
- Interleukin-38 promotes alveolar bone repair in periodontitis by suppressing the nuclear factor kappa B pathway.Stem cell research & therapy · 2026Article
- Impact of Anti-CD20 Therapies on Cytokine, Chemokine and Adhesion Molecule Dynamics in Multiple Sclerosis: A Narrative Review.Neurology and therapy · 2026Review
- Mesangial Cells (MES-SV40) Cultured in High Glucose Produce IL-36α, Which Is Associated with Type 2 Diabetes Mellitus.International journal of molecular sciences · 2026Article
- Mast Cells Accumulate in the Stroma of Breast Adenocarcinoma and Secrete Pro-Inflammatory Cytokines and Tumor-Damaging Mediators: Could IL-37 and IL-38 Play an Anti-Tumor Role?International journal of molecular sciences · 2026Review
- Elevated serum interleukin-38 levels in polymyositis and dermatomyositis: diagnostic implications and correlations with inflammatory markers.Frontiers in immunology · 2026Article
- The role of the bidirectional regulatory network between immune cells and stromal cells in cardiac repair and fibrosis following myocardial infarction.Frontiers in immunology · 2026Review
- Macrophage polarization in ischemia-reperfusion injury: from molecular mechanisms to therapeutic strategies.Frontiers in immunology · 2026Review
- The IL-36 Cytokine Rheostat: Hierarchical Regulation of Epithelial-Immune Crosstalk and Precision Therapy in Psoriatic and Related Dermatoses.Clinical, cosmetic and investigational dermatology · 2026Review
- Anti-Inflammatory Cytokine Signatures in Primary Glaucoma Subtypes: Diagnostic and Pathophysiological Insights From IL-36Ra, IL-37, and IL-38.Journal of ophthalmology · 2026Article
- IL-37 and IL-38 in sepsis: immune-metabolic rheostats in a dynamic inflammatory continuum.Frontiers in immunology · 2026Review
- IL-38 attenuates vascular calcification by upregulating GPX3-mediated antioxidant defense via the PPAR-γ/NRF2 axis.Cellular and molecular life sciences : CMLS · 2025Article
- IL-1 family cytokines in inflammation and immunity.Cellular & molecular immunology · 2025Review
- Review
125 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
The functional role of IL-1 family member 10, recently renamed IL-38, remains unknown. In the present study we aimed to elucidate the biological function of IL-38 and to identify its receptor. Heat-killed Candida albicans was used to stimulate memory T-lymphocyte cytokine production in freshly obtained human peripheral blood mononuclear cells from healthy subjects. The addition of recombinant IL-38 (152 amino acids) inhibited the production of T-cell cytokines IL-22 (37% decrease) and IL-17 (39% decrease). The reduction in IL-22 and IL-17 caused by IL-38 was similar to that caused by the naturally occurring IL-36 receptor antagonist (IL-36Ra) in the same peripheral blood mononuclear cells cultures. IL-8 production induced by IL-36γ was reduced by IL-38 (42% decrease) and also was reduced by IL-36Ra (73% decrease). When human blood monocyte-derived dendritic cells were used, IL-38 as well as IL-36Ra increased LPS-induced IL-6 by twofold. We screened immobilized extracellular domains of each member of the IL-1 receptor family, including the IL-36 receptor (also known as "IL-1 receptor-related protein 2") and observed that IL-38 bound only to the IL-36 receptor, as did IL-36Ra. The dose-response suppression of IL-38 as well as that of IL-36Ra of Candida-induced IL-22 and IL-17 was not that of the classic IL-1 receptor antagonist (anakinra), because low concentrations were optimal for inhibiting IL-22 production, whereas higher concentrations modestly increased IL-22. These data provide evidence that IL-38 binds to the IL-36R, as does IL-36Ra, and that IL-38 and IL-36Ra have similar biological effects on immune cells by engaging the IL-36 receptor.
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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.