白血球アラキドン酸代謝を介するeicosapentaenoic acidの抗炎症作用

抄録

Products derived from arachidonic acid (AA) via both the cyclooxygenase (particularly PGE₂) and lipoxygenase (particularly LTB₄) play a role in inflammation. To clarify the effect of eicosapentaenoic acid (EPA) on inflammation, EPA ethyl ester (80% pure, 240 mg/kg/day) was administered for 4 weeks to the rats. The supplementation of a standard rat diet with EPA caused a significant increase in the formation of LTB₅, which is biologically for less active (at least 30 times) than LTB₄, and a decrease in the synthesis of LTB₄ by A 23187 stimulated leukocytes. The EPA rich diet significantly increase the EPA content of leukocytes phospholipids without altering the content of AA, DHA and linoleic acid.
Then, antiinflammatory effect of EPA was assessed using two models of acute inflammation. In the first model EPA fed rat (240 mg/kg/day for 4 weeks) produced significantly lower concentration of PGE₂ and TXB₂ in inflammatory exudate derived from implantation of carrageenin impregnated sponges. Triene prostaglandin were not detected in the exudate however certain level of LTB₅ were present. In the second model, edema induced by injection of carrageenin into rat paws were significantly reduced in animals fed an EPA rich diet. Supplementation of the diet with EPA could, by reducing the synthesis of PGE₂ and LTB₄ and increasing LTB₅ (less active biologically), offer a novel and nontoxic approach to the modulation of an inflammatory response.
Further in vitro experiment disclosed that EPA was better substrate for 5-lipoxygenase than AA but was less favoured substrate for LTA hydrolase. EPA or its oxygenated metabolites, such as LTA₅ or LTB₅ inhibits LTB₄ formation particularly at the level of LTA hydrolase.