Abstract
The mechanism of the inhibitory effect of pranoprofen on sodium urate crystal-induced inflammation was investigated with several inflammatory parameters using leucocytes stimulated with sodium urate crystals in vitro. At 10-5M, pranoprofen tended to inhibit the production of chemotactic factor in guinea pig polymorphonuclear leucocytes (PMNL) stimulated with sodium urate crystals and at 10-4M, significantly inhibited it. At 10-3M and 10-4M, it potentiated the chemotaxis of guinea pig PMNL. Furthermore, it inhibited the production of superoxide anion (O2-) in guinea pig PMNL stimulated with sodium urate crystals, with an IC50 value of 5.0 × 10-4M, comparable to that of indomethacin. At 10-3M, it inhibited the release of β-glucuronidase stimulated by sodium urate crystals. From doses as low as 10-6M, it inhibited dose-dependently the production of PGE2-like substance by the phagocytosis of sodium urate crystals by rat peritoneal leucocytes, with an IC50 value of 7.5 × 10-6M. These results suggest that in inhibiting the production of PGE2 stimulated by sodium urate crystals, pranoprofen shows an inhibitory effect on sodium urate crystal-induced inflammation.