PROSTAGLANDIN E-2 PROTECTS AGAINST LIVER-INJURY AFTER ESCHERICHIA-COLI INFECTION BUT HAMPERS THE RESOLUTION OF THE INFECTION IN MICE

cAMP-increasing agents such as prostaglandin E-2 (PGE(2)) are known to protect against LPS-induced liver injury by downregulating the produc tion of inflammatory cytokines such as TNF-alpha. However, the effects of such reagents on host defense against bacterial infection remain u nknown, We show here that in vivo administration of PGE(2) significant ly protected mice against liver injury after Escherichia coli infectio n but hampered the resolution of the infection. PGE(2) significantly s uppressed circulating TNF-alpha and IL-12 levels but increased the IL- 10 production after E. coli challenge. PGE(2) inhibited the emergence of gamma delta T cells in the peritoneal cavity, which are important f or host defense against E, coli, and deteriorated bacterial exclusion in the peritoneal cavity after E. coli challenge. These results sugges ted that PGE(2) affects host defense mechanisms against E. coli infect ion through modulation of cytokine production and gamma delta T cell a ccumulation.