title: IL-33/ST2 correlates with severity of haemorrhagic fever with renal syndrome and regulates the inflammatory response in Hantaan virus-infected endothelial cells.
abstract: BACKGROUND
  Hantaan virus (HTNV) causes a severe lethal haemorrhagic fever with renal syndrome (HFRS) in humans. Despite a limited understanding of the pathogenesis of HFRS, the importance of the abundant production of pro-inflammatory cytokines has been widely recognized. Interleukin 33 (IL-33) has been demonstrated to play an important role in physiological and pathological immune responses. After binding to its receptor ST2L, IL-33 stimulates the Th2-type immune response and promotes cytokine production. Depending on the disease model, IL-33 either protects against infection or exacerbates inflammatory disease, but it is unknown how the IL-33/ST2 axis regulates the immune response during HTNV infection.
  
  
  RESULTS
  Blood samples were collected from 23 hospitalized patients and 28 healthy controls. The levels of IL-33 and soluble ST2 (sST2) in plasma were quantified by ELISA, and the relationship between IL-33, sST2 and the disease severity was analyzed. The role of IL-33/sST2 axis in the production of pro-inflammatory cytokines was studied on HTNV-infected endothelial cells. The results showed that the plasma IL-33 and sST2 were significantly higher in patients than in healthy controls. Spearman analysis showed that elevated IL-33 and sST2 levels were positively correlated with white blood cell count and viral load, while negatively correlated with platelet count. Furthermore, we found that IL-33 enhanced the production of pro-inflammatory cytokines in HTNV-infected endothelial cells through NF-κB pathway and that this process was inhibited by the recombinant sST2.
  
  
  CONCLUSIONS
  Our results indicate that the IL-33 acts as an initiator of the "cytokine storm" during HTNV infection, while sST2 can inhibit this process. Our findings could provide a promising immunotherapeutic target for the disease control.
authors: Department of Immunology, The Fourth Military Medical University, Xi'an, China.
authors: Yusi
authors: Y
authors: Zhang
authors: Department of Immunology, The Fourth Military Medical University, Xi'an, China.
authors: Chunmei
authors: C
authors: Zhang
authors: Department of Immunology, The Fourth Military Medical University, Xi'an, China.
authors: Ran
authors: R
authors: Zhuang
authors: Department of Immunology, The Fourth Military Medical University, Xi'an, China.
authors: Ying
authors: Y
authors: Ma
authors: Department of Immunology, The Fourth Military Medical University, Xi'an, China.
authors: Yun
authors: Y
authors: Zhang
authors: Department of Immunology, The Fourth Military Medical University, Xi'an, China.
authors: Jing
authors: J
authors: Yi
authors: Department of Immunology, The Fourth Military Medical University, Xi'an, China.
authors: Angang
authors: A
authors: Yang
authors: Department of Immunology, The Fourth Military Medical University, Xi'an, China.
authors: Boquan
authors: B
authors: Jin
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D018063:Hantaan virus / Q000276:immunology*; D006480:Hemorrhagic Fever with Renal Syndrome / Q000276:immunology* / Q000473:pathology / Q000821:virology; D061307:Human Umbilical Vein Endothelial Cells / Q000276:immunology / Q000378:metabolism / Q000821:virology; D006801:Humans; D007249:Inflammation / Q000276:immunology; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33 / Q000097:blood / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D034622:RNA Interference; D034741:RNA, Small Interfering; D011956:Receptors, Cell Surface / Q000097:blood / Q000235:genetics / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology; D051996:Transcription Factor RelA / Q000235:genetics / Q000276:immunology*; D019562:Viral Load / Q000276:immunology
chemical_list: C079241:IL1RL1 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; C498143:RELA protein, human; D034741:RNA, Small Interfering; D011956:Receptors, Cell Surface; D051996:Transcription Factor RelA