Prostaglandin E series (PGEs) are known to protect against lipopolysaccharide (LPS)-induced liver injury by down-regulating the production of inflammatory cytokines. We show here a novel mechanism whereby prostaglandin E1 protects mice against liver injury after Escherichia coli infection. Prostaglandin E1 administration suppressed circulating interleukin 12 (IL-12) levels but increased the IL-10 production after E. coli challenge. Furthermore, prostaglandin E1-α-cyclodextrin (PGE1) shifted the Th1/Th2 balance of CD3(intermediate) IL-2Rβ+ T cells in the liver to a dominant Th2-like response. Neutralization of endogenous IL-4 by administration of anti-IL-4 monoclonal antibody (mAb) diminished the inhibitory effect of prostaglandin E1 on liver injury after E. coli challenge. These results suggested that the Th2-like response of liver T cells may be at least partly involved in the mechanism whereby prostaglandin E1 protects against E. coli-induced liver injury.
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