Abstract
Interleukin (IL)-33 is a member of the IL-1 family, which plays an important role in inflammatory response. In this study, we evaluated the effect of IL-33 on septicemia and the underlying mechanisms by establishing a Staphylococcus epidermidis (S. epidermidis)-induced septicemic mouse model. The expression of IL-33, IL-1α, IL-1β, IL-6, IL-17A, IL-22, and PGE2 were measured by double antibody sandwich enzyme-linked immunosorbent assay, and bacterial colony formation in peripheral blood and kidneys were counted postinfection. The percentages of neutrophils, eosinophils, and inflammatory monocytes were evaluated by flow cytometry, and tissue damage was assessed by hematoxylin and eosin (H&E) staining. The survival of septicemic mice was monitored daily. IL-33 expression was significantly augmented following S. epidermidis infection. High IL-33 expression significantly decreased the survival of model mice, and aggravated the damage of lung, liver, and kidney tissues. However, administration of ST2 (receptor for IL-33) to the S. epidermidis-infected mice blocked the IL-33 signaling pathway, which elevated PGE2, IL-17A, and IL-22, and promoted healing of organ damage. In addition, ST2 suppressed the mobilization of inflammatory monocytes, but promoted the accumulation of neutrophils and eosinophils in S. epidermidis-infected mice. Inhibition of PGE2, IL-17A, and IL-22 facilitated the development of septicemia and organ damage in S. epidermidis-infected mice, as well as reducing their survival. Our findings reveal that IL-33 aggravates organ damage in septicemic mice by inhibiting PGE2, IL-17A, and IL-22 production.