ArticleArthritis and rheumatism2013
Interferon-γ mediates anemia but is dispensable for fulminant toll-like receptor 9-induced macrophage activation syndrome and hemophagocytosis in mice.
Article in Arthritis and rheumatism, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers, 1 of them a synthesis that pooled it.
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Who cites it
70 citing papers in PubMed, 1 synthesis or guideline pooled it, 114 citations in OpenAlex.
- Update in Hyperferritinemic Syndromes: Recognition and Management - A Scoping Review.The Brown journal of hospital medicine · 2022Pooled it
- 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
- A Multifaceted Interplay Among Hemophagocytosis, Interleukin-18, and Type I Interferon Distinguishes Still Disease From Other Autoinflammatory Diseases.Arthritis & rheumatology (Hoboken, N.J.) · 2026Article
- Loss of IL10 Signaling Promotes TLR9-Driven Liver Dysfunction by Allowing T Cell Receptor-Mediated T Cell Activation.Research square · 2026Article
- Free IL-18 in NLRC4-associated autoinflammatory disease without macrophage activation syndrome.Rheumatology (Oxford, England) · 2026Article
- STAT1 drives the immune landscape of murine Toll-like receptor 9-induced liver inflammation.JHEP reports : innovation in hepatology · 2026Article
- PRMT5 inhibition reduces hyperinflammation in a murine model of secondary hemophagocytic lymphohistiocytosis.Blood advances · 2025Article
- T-ing up the storm: pathogenic cycling lymphocytes in the biology of macrophage activation syndrome.Pediatric rheumatology online journal · 2025Review
- Tislelizumab-induced hemophagocytic lymphohistiocytosis in a patient with microsatellite instability-high colon cancer and coexisting systemic lupus erythematosus: a case report and literature review.Frontiers in oncology · 2025Article
- Malaria and dyserythropoiesis: a mini review.Frontiers in cellular and infection microbiology · 2025Review
- Turmeric andJournal of inflammation research · 2025Article
- Hemophagocytic lymphohistiocytosis: current treatment advances, emerging targeted therapy and underlying mechanisms.Journal of hematology & oncology · 2024Review
- The NLRP3 inflammasome is essential for IL-18 production in a murine model of macrophage activation syndrome.Disease models & mechanisms · 2024Article
- Article
- α2-Antiplasmin is associated with macrophage activation and fibrin deposition in a macrophage activation syndrome mouse model.Clinical and experimental immunology · 2024Article
- The NLRP3 inflammasome is essential for IL-18 production in a murine model of macrophage activation syndrome.bioRxiv : the preprint server for biology · 2024Article
- Cytokine Storm Syndrome Associated with Systemic Juvenile Idiopathic Arthritis.Advances in experimental medicine and biology · 2024Review
- Murine Models of Secondary Cytokine Storm Syndromes.Advances in experimental medicine and biology · 2024Review
- JAK Inhibitors in Cytokine Storm Syndromes.Advances in experimental medicine and biology · 2024Review
- Identification of miRNAs that target Fcγ receptor-mediated phagocytosis during macrophage activation syndrome.Frontiers in immunology · 2024Article
10 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveMacrophage activation syndrome (MAS) is a devastating cytokine storm syndrome complicating many inflammatory diseases and characterized by fever, pancytopenia, and systemic inflammation. It is clinically similar to hemophagocytic lymphohistiocytosis (HLH), which is caused by viral infection of a host with impaired cellular cytotoxicity. Murine models of MAS and HLH illustrate that interferon-γ (IFNγ) is the driving stimulus for hemophagocytosis and immunopathology. This study was undertaken to investigate the inflammatory contributors to a murine model of Toll-like receptor 9 (TLR-9)-induced fulminant MAS.
methodsWild-type, transgenic, and cytokine-inhibited mice were treated with an IL-10 receptor blocking antibody and a TLR-9 agonist, and parameters of MAS were evaluated.
resultsFulminant MAS was characterized by dramatic elevations in IFNγ, IL-12, and IL-6 levels. Increased serum IFNγ levels were associated with enhanced IFNγ production within some hepatic cell populations but also with decreased numbers of IFNγ-positive cells. Surprisingly, IFNγ-knockout mice developed immunopathology and hemophagocytosis comparable to that seen in wild-type mice. However, IFNγ-knockout mice did not become anemic and had greater numbers of splenic erythroid precursors. IL-12 neutralization phenocopied disease in IFNγ-knockout mice. Interestingly, type I IFNs contributed to the severity of hypercytokinemia and weight loss, but their absence did not otherwise affect MAS manifestations.
conclusionThese data demonstrate that both fulminant MAS and hemophagocytosis can arise independently of IFNγ, IL-12, or type I IFNs. They also suggest that IFNγ-mediated dyserythropoiesis, not hemophagocytosis, is the dominant cause of anemia in fulminant TLR-9-induced MAS. Thus, our data establish a novel mechanism for the acute anemia of inflammation, but suggest that a variety of triggers can result in hemophagocytic disease.
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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.