IL-33/ST2 Correlates with Severity of Haemorrhagic Fever with Renal Syndrome and Regulates the Inflammatory Response in Hantaan Virus-Infected Endothelial Cells

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. 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. 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. © 2015 zhang et al.