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-alpha. 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-alpha and IL-12 levels but increased the IL-10 production after E. coli challenge. PGE2 inhibited the emergence of gammadelta 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 gammadelta T cell accumulation.
Takano
M
M
Laboratory of Host Defense and Germfree Life, Research Institute for Disease Mechanism and Control, Nagoya University School of Medicine, Japan.
Nishimura
H
H
Kimura
Y
Y
Washizu
J
J
Mokuno
Y
Y
Nimura
Y
Y
Yoshikai
Y
Y
D000818:Animals; D002465:Cell Movement / Q000276:immunology; D015232:Dinoprostone / Q000494:pharmacology*; D004926:Escherichia coli / Q000254:growth & development; D004927:Escherichia coli Infections / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D007274:Injections, Intraperitoneal; D016753:Interleukin-10 / Q000097:blood; D018664:Interleukin-12 / Q000097:blood; D008070:Lipopolysaccharides / Q000633:toxicity; D008099:Liver / Q000187:drug effects / Q000382:microbiology / Q000473:pathology*; D008107:Liver Diseases / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008809:Mice, Inbred C3H; D010529:Peritoneal Cavity / Q000382:microbiology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000096:biosynthesis; D016176:T-Lymphocyte Subsets / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D008070:Lipopolysaccharides; D016692:Receptors, Antigen, T-Cell, gamma-delta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D015232:Dinoprostone