Macrolide antibiotics inhibit prostaglandin E2 synthesis and mRNA expression of prostaglandin synthetic enzymes in human leukocytes

We investigated the action of macrolide antibiotics, which are considered to have anti-inflammatory activity, on lipopolysaccharide (LPS)-stimulated prostaglandin (PG) E₂ synthesis and the expression of mRNAs for cytosolic phospholipase A₂ (cPLA₂), cyclooxygenase (COX)-1, and COX-2 in human leukocytes. The production of LPS-stimulated PGE₂ was significantly increased in peripheral polymorphonuclear leukocytes (PMNLs) and in mononuclear leukocytes (MNLs). Amounts of mRNAs for COX-2 and cPLA₂, but not for COX-1, were enhanced by LPS in PMNLs and MNLs. The LPS-enhanced PGE₂ synthesis and the expression of cPLA₂ and COX-2 mRNAs were inhibited by clarithromycin, azithromycin and dexamethasone in PMNLs and MNLs. The mRNA expression of COX-1 in PMNLs was decreased by clarithromycin and azithromycin. Macrolide antibiotics inhibited PGE₂ synthesis in human leukocytes by suppressing cPLA₂, COX-1, and COX-2 mRNA expression. These data indicate one mechanism of macrolide anti-inflammatory activity.