ArticleThe Journal of allergy and clinical immunology2022
Excessive IL-10 and IL-18 trigger hemophagocytic lymphohistiocytosis-like hyperinflammation and enhanced myelopoiesis.
Article in The Journal of allergy and clinical immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 30 citations in OpenAlex.
- The IL-10/IL-6 Ratio and the Risk Score: Two Cytokines-Based Predictors for Malignancy-Associated Hemophagocytic Lymphohistiocytosis in Adults (M-HLHa).American journal of hematology · 2026Observational
- Single-cell profiling of natural killer/T-cell lymphoma reveals stratified immune features and potential therapeutic implications.Nature communications · 2026Article
- Type I Interferon-Driven Monocyte Dysregulation and MAS-associated CD8bioRxiv : the preprint server for biology · 2026Article
- Chimeric antigen receptor T-cell therapies related to immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome: Diagnosis, high-risk factors, and management.Chinese medical journal · 2026Review
- EBV DNA load and cytokines guide risk-stratified treatment in pediatric EBV-associated hemophagocytic lymphohistiocytosis.Virology journal · 2026Article
- Serum Cytokine Profiling Differentiates Underlying Diseases in Cytokine Storm Syndrome.Arthritis & rheumatology (Hoboken, N.J.) · 2026Article
- Early Prediction Model for Etoposide-Based Protocols Resistance in Pediatric HLH.Pediatric health, medicine and therapeutics · 2026Article
- Immune dysregulation and exhaustion in EBV- associated hemophagocytic lymphohistiocytosis: insights from single-cell transcriptomics and TCR repertoire analysis.Frontiers in immunology · 2026Article
- Visceral Leishmaniasis-Associated Hemophagocytic Lymphohistiocytosis in a Patient With Crohn's Disease in Therapy With Anti-TNFα: A Challenging Diagnostic Case Report.Case reports in gastrointestinal medicine · 2026Article
- C3 as a predictive and prognostic biomarker in adult hemophagocytic lymphohistiocytosis: a large cohort study in China.Blood advances · 2025Article
- Deep insight into cytokine storm: from pathogenesis to treatment.Signal transduction and targeted therapy · 2025Review
- The pathophysiology of hemophagocytic lympho-histiocytosis (HLH) syndrome and insights from animal models.Clinical and experimental immunology · 2025Review
- Study on the therapeutic effect of Viola yedoensis and Leonurus japonicus on bovine endometritis.Journal of animal science · 2025Article
- Hemophagocytic lymphohistiocytosis: current treatment advances, emerging targeted therapy and underlying mechanisms.Journal of hematology & oncology · 2024Review
- The assembly of neutrophil inflammasomes during COVID-19 is mediated by type I interferons.PLoS pathogens · 2024Article
- Article
- The GFPT2-O-GlcNAcylation-YBX1 axis promotes IL-18 secretion to regulate the tumor immune microenvironment in pancreatic cancer.Cell death & disease · 2024Article
- A predictive model for Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis.Frontiers in immunology · 2024Article
- Into the storm: the imbalance in the yin-yang immune response as the commonality of cytokine storm syndromes.Frontiers in immunology · 2024Review
- Neutrophil extracellular trap-induced intermediate monocytes trigger macrophage activation syndrome in adult-onset Still's disease.BMC medicine · 2023Article
Corrections and comments
- Erratum issuedCorrigenda.2026
Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundHyperinflammation is a life-threatening condition associated with various clinical disorders characterized by excessive immune activation and tissue damage. Multiple cytokines promote the development of hyperinflammation; however, the contribution of IL-10 remains unclear despite emerging speculations for a pathological role. Clinical observations from hemophagocytic lymphohistiocytosis (HLH), a prototypical hyperinflammatory disease, suggest that IL-18 and IL-10 may collectively promote the onset of a hyperinflammatory state.
objectiveWe aimed to investigate the collaborative roles of IL-10 and IL-18 in hyperinflammation.
methodsA comprehensive plasma cytokine profile for 87 secondary HLH patients was first depicted and analyzed. We then investigated the systemic and cellular effects of coelevated IL-10 and IL-18 in a transgenic mouse model and cultured macrophages. Single-cell RNA sequencing was performed on the monocytes/macrophages isolated from secondary HLH patients to explore the clinical relevance of IL-10/IL-18-mediated cellular signatures. The therapeutic efficacy of IL-10 blockade was tested in HLH mouse models.
resultsExcessive circulating IL-10 and IL-18 triggered a lethal hyperinflammatory disease recapitulating HLH-like phenotypes in mice, driving peripheral lymphopenia and a striking shift toward enhanced myelopoiesis in the bone marrow. IL-10 and IL-18 polarized cultured macrophages to a distinct proinflammatory state with pronounced expression of myeloid cell-recruiting chemokines. Transcriptional characterization suggested the IL-10/IL-18-mediated cellular features were clinically relevant with HLH, showing enhanced granzyme expression and proteasome activation in macrophages. IL-10 blockade protected against the lethal disease in HLH mouse models.
conclusionCoelevated IL-10 and IL-18 are sufficient to drive HLH-like hyperinflammatory syndrome, and blocking IL-10 is protective in HLH models.
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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.