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.
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.
Chiba
K
K
Eisai Tsukuba Research Laboratories, Ibaraki, Japan.
Goto
M
M
Shirota
H
H
D000179:Acrylates / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism; D005122:Exudates and Transudates / Q000166:cytology / Q000378:metabolism; D006099:Granuloma / Q000378:metabolism / Q000517:prevention & control*; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000096:biosynthesis*; D008297:Male; D009284:Naphthols / Q000494:pharmacology*; D009961:Orosomucoid / Q000096:biosynthesis; D011239:Prednisolone / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344
D000179:Acrylates; D000894:Anti-Inflammatory Agents, Non-Steroidal; D007375:Interleukin-1; D009284:Naphthols; D009961:Orosomucoid; C069676:E 5090; D011239:Prednisolone; D015232:Dinoprostone; D007213:Indomethacin