EFFECTS OF JTE-522, A SPECIFIC INHIBITOR OF CYCLOOXYGENASE-2, ON THE RECURRENCE OF ALLERGIC INFLAMMATION IN RATS

JTE-522, l-2-methyloxazol-5-yl)-2-fluorobenzenesulfonamide, is a selec tive inhibitor of cyclooxygenase-2 at the enzyme level (IC50 is 6.4 x 10(-7) M for sheep cyclooxygenase-2, but it does not inhibit sheep cyc looxygenase-1 at concentrations up to 10(-4) M). In rat peritoneal mac rophages in culture, it markedly inhibited cyclooxygenase-2-dependent prostaglandin E-2 production and weakly inhibited cyclooxygenase-1-dep endent prostaglandin E-2 production, as did the selective cyclooxygena se-2 inhibitor NS-398 cyclohexyloxy-4-nitrophenyl)]-methanesulfonamide ). In addition, the anti-inflammatory activity of JTE-522 was evaluate d, using a model of recurrent air pouch-type allergic inflammation in rats. JTE-522, injected into the pouch just after a second antigen cha llenge, suppressed the accumulation of pouch fluid, the infiltration o f leukocytes and the prostaglandin E-2 content in the pouch fluid: as did NS-398 and indomethacin. These findings indicated that JTE-522 is a selective cyclooxygenase-2 inhibitor in cell culture systems and tha t the suppression by JTE-522 of the recurrence of allergic inflammatio n is due to the inhibition of cyclooxygenase-2. (C) 1998 Elsevier Scie nce B.V.