Sepsis is a systemic immune response to infection. In patients with sepsis, many symptoms such as organ dysfunction, hypotension, hypothermia, or fever, increased level of leukocytes, and tachycardia are observed. 1 The hallmark pathological feature of sepsis is the infiltration of inflammatory leukocytes into multiple organs. Macrophages are the fast immune cells to phagocyte pathogens. These macrophages produce pro-inflammatory cytokines [eg, tumor necrosis factor (TNF)-α, interleukin (IL)-1, and IL-6] to induce the infiltration of other immune cells such as neutrophils. 2 Neutrophils also kill pathogens by producing oxidase-derived reactive oxygen species (ROS), cytotoxic granule components, antimicrobial peptides, and neutrophil extracellular traps (NETs). 3 Continuing or overproduction of pro-inflammatory cytokines, ROS, and NETs in macrophages and neutrophils caused tissue damages, and the incidence of severe sepsis and septic shock was increased. In

Sepsis is systemic inflammatory response syndrome caused by invasive infection. Although it is known that prostaglandin (PG)F 2α level is elevated in the plasma of the patients with sepsis, its role in the sepsis remains unclear. We aimed to investigate the role of PGF 2α receptor (FP) signaling in lipopolysaccharide (LPS)-induced sepsis using FP receptor antagonist AL8810 in mice. Sepsis was induced by intraperitoneal injection of LPS (5 mg/kg). AL8810 (10 mg/kg) was intraperitoneally administered at 30 min before LPS injection. Mice were monitored to detect the response to LPS for 24 hours. LPS administration promoted PGF 2α production in peritoneal lavage fluid (PLF). At 6 hours after LPS administration, the number of macrophages and neutrophils in PLF was increased, as compared with naïve mice. AL8810 administration enhanced neutrophil migration, but not macrophage migration, in PLF. At 24 hours after injection, there was no difference in number of these cells between LPS and/or AL8810-administered mice. At 24 hours after LPS administration, the mRNA expression of proinflammatory cytokines such as IL-6, TNFα, IL-1β, and CXCL2 in lung and liver was elevated. Conversely, they were decreased in AL8810-administered mice. It is known that IL-10 decreased excessive inflammatory responses in the acute phase of sepsis. At 3-6 hours after LPS administration, IL-10 levels in PLF were increased, as compared with naïve mice. AL8810 administration enhanced IL-10 production further. In addition, immunostaining showed that Gr-1-positive neutrophils in PLF expressed IL-10. Then, anti-IL-10 antibody administration increased LPS-induced IL-6 and CXCL-2 expression as well as AL8810-decreased these gene expressions. The findings suggest that FP receptor antagonist attenuated LPSinduced sepsis by increasing neutrophil-derived anti-inflammatory cytokine IL-10 production.