Prostaglandin E₁ protects against liver injury induced by Escherichia coli infection via a dominant Th2-like response of liver T cells in mice

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.