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.