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- W4381619118 abstract "Background Interleukin (IL)-18 and IL-1β play a central role in the pathogenesis of systemic juvenile idiopathic arthritis (s-JIA) and its life-threatening complication, macrophage activation syndrome (MAS). Objectives This study aimed to clarify the role of IL-18 and IL-1β in the pathogenesis of MAS. Methods We developed a mouse model to evaluate the role of each cytokine with toll-like receptor 9 stimulation after continuous infusion with IL-18, IL-1β, and a combination of both for 7 days. The symptoms and laboratory findings were compared among IL-18, IL-1β, and combination groups. Results Body weight was significantly decreased in the IL-1β and the combination groups. Splenomegaly was observed in all groups, whereas hepatomegaly was noted in IL-18 group only. Decreased T cell numbers, anemia, and thrombocytopenia were observed in the combination group. IFN-γ, CXCL9, and IL-12A mRNA levels were upregulated and IL-10 mRNA levels in the spleen were downregulated in the IL-18 group. Hepatomegaly and splenomegaly in the IL-18 group were observed in a dose-dependent manner. TNF-α, CXCL9, and IL-12A mRNA levels were upregulated only in mice with extremely elevated plasma IL-18 levels. Conclusion IL-18 and IL-1β have distinct roles in the pathogenesis of MAS. Dual blockade of IL-18 and IL-1β might be necessary to treat MAS." @default.
- W4381619118 created "2023-06-23" @default.
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- W4381619118 date "2023-06-01" @default.
- W4381619118 modified "2023-10-17" @default.
- W4381619118 title "Distinct roles of IL-18 and IL-1β in murine model of macrophage activation syndrome" @default.
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- W4381619118 doi "https://doi.org/10.1016/j.jaci.2023.05.027" @default.
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