ArticleArthritis & rheumatology (Hoboken, N.J.)2014
Systemic juvenile idiopathic arthritis-like syndrome in mice following stimulation of the immune system with Freund's complete adjuvant: regulation by interferon-γ.
Article in Arthritis & rheumatology (Hoboken, N.J.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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47 citing papers in PubMed, 92 citations in OpenAlex.
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- Monocyte/macrophages may exert prominent roles in macrophage activation syndrome.Annals of hematology · 2025Article
- Metabolic Reprogramming in Response to Freund's Adjuvants: Insights from Serum Metabolomics.Microorganisms · 2025Article
- The unique activity of the bone morphogenetic protein TGH4 affects the embryonic development of Trichinella spiralis and the establishment of vaccine protection.Veterinary research · 2025Article
- The pathophysiology of hemophagocytic lympho-histiocytosis (HLH) syndrome and insights from animal models.Clinical and experimental immunology · 2025Review
- Comprehensive safety assessment and therapeutic potential of Pediococcus acidilactici NMCC-B in attenuating arthritis progression.PloS one · 2025Article
- Recent advances and evolving concepts in Still's disease.Nature reviews. Rheumatology · 2024Review
- Monocytic Phagocytes in the Immunopathogenesis of Cytokine Storm Syndromes.Advances in experimental medicine and biology · 2024Review
- Heterogeneity of macrophage activation syndrome and treatment progression.Frontiers in immunology · 2024Review
- Identification of miRNAs that target Fcγ receptor-mediated phagocytosis during macrophage activation syndrome.Frontiers in immunology · 2024Article
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- Identification of immune cell infiltration and effective biomarkers of polycystic ovary syndrome by bioinformatics analysis.BMC pregnancy and childbirth · 2023Article
- Mouse models of systemic juvenile idiopathic arthritis and macrophage activation syndrome.Arthritis research & therapy · 2023Review
- A review of the pleiotropic actions of the IFN-inducible CXC chemokine receptor 3 ligands in the synovial microenvironment.Cellular and molecular life sciences : CMLS · 2023Review
- Current status of hand-foot-and-mouth disease.Journal of biomedical science · 2023Review
- Systemic Juvenile Idiopathic Arthritis/Pediatric Still's Disease, a Syndrome but Several Clinical Forms: Recent Therapeutic Approaches.Journal of clinical medicine · 2022Article
- Cytokine Storm in COVID-19: Immunopathogenesis and Therapy.Medicina (Kaunas, Lithuania) · 2022Review
- The Role of Interleukin 18/Interleukin 18-Binding Protein in Adult-Onset Still's Disease and Systemic Juvenile Idiopathic Arthritis.Journal of clinical medicine · 2022Review
- A preliminary study on the characteristics of Th1/Th2 immune response in cerebrospinal fluid of AIDS patients with cryptococcal meningitis.BMC infectious diseases · 2021Article
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Authors and funding
13 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveSystemic juvenile idiopathic arthritis (JIA) is unique among the rheumatic diseases of childhood, given its distinctive systemic inflammatory character. Inappropriate control of innate immune responses following an initially harmless trigger is thought to account for the excessive inflammatory reaction. The aim of this study was to generate a similar systemic inflammatory syndrome in mice by injecting a relatively innocuous, yet persistent, immune system trigger: Freund's complete adjuvant (CFA), containing heat-killed mycobacteria.
methodsGiven the central role of interferon-γ (IFNγ) in immune regulation, we challenged wild-type (WT) and IFNγ-knockout (KO) BALB/c mice with CFA, and analyzed their clinical symptoms and biologic characteristics. The production of cytokines and the effects of anticytokine antibodies were investigated.
resultsIn WT mice, CFA injection resulted in splenomegaly, lymphadenopathy, neutrophilia, thrombocytosis, and increased cytokine expression. In the absence of IFNγ, these symptoms were more pronounced and were accompanied by weight loss, arthritis, anemia, hemophagocytosis, abundance of immature blood cells, and increased levels of interleukin-6 (IL-6), all of which are reminiscent of the symptoms of systemic JIA. CFA-challenged IFNγ-KO mice showed increased expression of IL-17 by CD4+ T cells and by innate γ/δ T cells. Inflammatory and hematologic changes were prevented by treatment with anti-IL-12/IL-23p40 and anti-IL-17 antibodies.
conclusionImmune stimulation of IFNγ-KO mice with CFA produces a systemic inflammatory syndrome reflecting the clinical, biologic, and histopathologic picture of systemic JIA. The protective function of IFNγ in preventing anemia and overall systemic inflammation is a striking observation. The finding that both adaptive and innate T cells are important sources of IL-17 may be of relevance in the pathogenesis of systemic JIA.
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