Ketamine inhibits the phagocytic responses of canine peripheral blood polymorphonuclear cells through the upregulation of prostaglandin E2 in peripheral blood mononuclear cells in vitro

Ketamine has been reported to decrease the immune functions of phagocytes. Previously, we observed that the phagocytic capacity and oxidative burst activity (OBA) of canine peripheral blood polymorphonuclear cells (PMNs) were inhibited by the supernatant from canine peripheral blood mononuclear cells (PBMCs) cultures treated with ketamine. In the present study, we examined whether in vitro treatment with ketamine modulates prostaglandin E₂ (PGE₂) production in PBMCs. Treatment with ketamine or with ketamine-treated PBMCs culture supernatant simultaneously decreased the phagocytic capacity and OBA of PMNs. Ketamine increased PGE₂ production by PBMCs. Recombinant PGE₂ decreased the phagocytic capacity and OBA of PMNs. AH-6809, an E-prostanoid 2 (EP2) antagonist, restored the phagocytic capacity and OBA of PMNs, decreased by either the ketamine-treated PBMCs culture supernatant or recombinant PGE₂. These results suggest that ketamine inhibits the phagocytic responses of canine PMNs, and that this results from the increase in PGE₂ produced by canine PBMCs.