Prostaglandin E₂ protects against liver injury after Escherichia coli infection but hampers the resolution of the infection in mice

cAMP-increasing agents such as prostaglandin E₂ (PGE₂) are known to protect against LPS-induced liver injury by downregulating the production of inflammatory cytokines such as TNF-α. However, the effects of such reagents on host defense against bacterial infection remain unknown. We show here that in vivo administration of PGE₂ significantly protected mice against liver injury after Escherichia coli infection but hampered the resolution of the infection. PGE₂ significantly suppressed circulating TNF-α and IL-12 levels but increased the IL-10 production after E. coli challenge. PGE₂ inhibited the emergence of γδ T cells in the peritoneal cavity, which are important for host defense against E. coli, and deteriorated bacterial exclusion in the peritoneal cavity after E. coli challenge. These results suggested that PGE₂ affects host defense mechanisms against E. coli infection through modulation of cytokine production and γδ T cell accumulation.