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  • Title: Interleukin-33/ST2 signaling contributes to the severity of hemolytic uremic syndrome induced by enterohemorrhagic Escherichia coli.
    Author: Yamada S, Shimizu M, Kuroda M, Inoue N, Sugimoto N, Yachie A.
    Journal: Clin Exp Nephrol; 2019 Apr; 23(4):544-550. PubMed ID: 30467800.
    Abstract:
    OBJECTIVES: Interleukin (IL)-33 plays an important role in host defense, immune regulation, and inflammation. This study assessed IL-33's role in the pathogenesis of severe hemolytic uremic syndrome (HUS) induced by enterohemorrhagic Escherichia coli (EHEC). We also investigated the clinical significance of IL-33 and soluble ST2 (soluble form of IL-33 receptor) serum levels in patients with EHEC-induced HUS. METHODS: The role of IL-33 in Shiga toxin (STx)-2-induced endothelial injury was studied in human umbilical vein endothelial cells (HUVECs) in vitro. Blood samples were obtained from 21 HUS patients and 15 healthy controls (HC). The IL-33 and sST2 serum levels were quantified using an enzyme-linked immunosorbent assay. The results were compared to HUS' clinical features. RESULTS: Cytotoxic assays indicated that IL-33 enhanced STx2 toxicity in HUVECs. Serum IL-33 levels in most HUS patients were below the lowest detection limit. On the other hand, serum sST2 levels in patients during the HUS phase were significantly higher than those in HC and showed a correlation with disease severity. Serum sST2 levels in patients with encephalopathy were significantly higher than those in patients without it. A serum sST2 level > 63.2 pg/mL was associated with a high risk of encephalopathy. Serum sST2 levels significantly correlated with serum levels of inflammatory cytokines related to the development of HUS. CONCLUSIONS: Our results indicate that IL-33 contributes to the severity of EHEC-induced HUS. Serum sST2 level in HUS patients correlated with disease activity, which suggests its potential role as a marker for disease activity and development of encephalopathy in patients with EHEC-induced HUS.
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