Mechanisms of antagonism of interleukin-1 alpha by synthetic interleukin-1 blockers.
A series of interleukin-1 blockers, CK-compounds, were shown to inhibit the dose-response curve of IL-1 induced uveitis in a non-competitive manner. CK-compounds showed little or weak effects on PGE2 production, leukocyte chemotaxis, and lipoxygenase activity which were markedly inhibited by indomethacin, REV 9501, and NDGA, respectively. These results indicate that CK-compounds do not fall into the conventional class of non-steroidal arachidonate mediated anti-inflammatory agents. CK-compounds should therefore be classified as novel compounds to block IL-1 non-competitively and belong to non-steroidal, non-arachidonate mediated anti-inflammatory agents.
Xiao
J G
JG
Institute of Ocular Pharmacology, Texas A&M University College of Medicine, College Station, USA.
Schwade
N
N
Chiou
G C
GC
D000287:Administration, Topical; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D003459:Crystallins; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005123:Eye / Q000378:metabolism; D005260:Female; D007375:Interleukin-1 / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D007958:Leukocyte Count; D008084:Lipoxygenase / Q000378:metabolism; D008297:Male; D009883:Ophthalmic Solutions; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D014602:Uvea; D014605:Uveitis / Q000209:etiology / Q000517:prevention & control*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003459:Crystallins; D007375:Interleukin-1; D009883:Ophthalmic Solutions; D008084:Lipoxygenase; D015232:Dinoprostone