A novel inhibitor of IL-1 generation, E5090: in vivo inhibitory effect on the generation of IL-1-like factor and on granuloma formation in an air-pouch model

Abstract

The in vivo production of IL-1-like activity was investigated in the exudate of a rat air-pouch inflammatory model. An inflammatory reaction was induced by LPS injection into the air-pouch. IL-1 activity in the exudate reached the maximum level at 4 h and then rapidly decreased until 8 h after the injection of LPS. Orally administered E5090 and prednisolone dose-dependently inhibited the generation of IL-1 activity. Both compounds also suppressed chronic granuloma formation in parallel with the IL-1 inhibition. On the other hand, indomethacin had no effect on either IL-1 generation or granuloma formation in spite of the complete inhibition of PGE2 generation. These results suggest that E5090 inhibits the production of IL-1-like activity in the exudate and exhibits steroid-like antiinflammatory effects.