• Cyclo-oxygenase;
  • prostaglandins;
  • inflammation;
  • COX-2
  • Cyclo-oxygenase-2 (COX-2) is expressed at sites of inflammation and is believed to be the major source of inflammation-associated prostaglandin synthesis. Selective inhibition of COX-2 has been suggested to produce anti-inflammatory effects with reduced toxicity in the gastrointestinal tract. We examined the extent to which suppression of COX-2 led to inhibition of various components of inflammation in the carrageenan-airpouch model in the rat.

  • Indomethacin (geqslant R: gt-or-equal, slanted0.3 mg kg−1), nimesulide (geqslant R: gt-or-equal, slanted3 mg kg−1) and the selective COX-2 inhibitor, SC-58125 (geqslant R: gt-or-equal, slanted0.3 mg kg−1), significantly suppressed the production of prostaglandin E2 at the site of inflammation. At higher doses, indomethacin (geqslant R: gt-or-equal, slanted1 mg kg−1) and nimesulide (30 mg kg−1), but not SC-58125 (up to 10 mg kg−1), significantly inhibited COX-1 activity (as measured by whole blood thromboxane synthesis).

  • All three test drugs significantly reduced the volume of exudate in the airpouch, but only at doses greater than those required for substantial (>90%) suppression of COX-2 activity. Similarly, reduction of leukocyte infiltration was only observed with the doses of indomethacin and nimesulide that caused significant suppression of COX-1 activity.

  • SC-58125 did not significantly affect leukocyte infiltration into the airpouch at any dose tested (up to 10 mg kg−1). A second selective COX-2 inhibitor, Dup-697, was also found to suppress exudate PGE2 levels without significant effects on leukocyte infiltration.

  • These results indicate that selective inhibition of COX-2 results in profound suppression of PGE2 synthesis in the carrageenan-airpouch, but does not affect leukocyte infiltration. Exudate volume was only reduced with the highly selective COX-2 inhibitor when a dose far above that necessary for suppression of COX-2 activity was used. Inhibition of leukocyte infiltration was observed with indomethacin and nimesulide, but only at doses that inhibited both COX-1 and COX-2.

British Journal of Pharmacology (1999) 126, 1200–1204; doi:10.1038/sj.bjp.0702420