Prevention of ocular inflammation induced by lens protein, endotoxin, and interleukin-1 with synthetic interleukin-1 blockers.
It is well known that corticosteroids are potent anti-inflammatory agents, yet they produce serious side effects. Although arachidonate metabolite blockers have been developed for the treatment of inflammation, they are much less potent than corticosteroids. Furthermore, they still process serious side effects. In search of potent and safe non-steroidal anti-inflammatory agents (NSAIA), interleukin-1 (IL-1) blockers have been developed. Among 121 CK-analogs studied, CK-17, CK-101A and CK103A have been identified as promising anti-inflammatory agents as potent as prednisolone in inhibiting lens proteins-induced inflammation and twice as potent as prednisolone in inhibiting endotoxin-and IL-1-induced uveitis. No serious side effects could be noticed with the doses of these compounds tested to date. These results indicate that the development of potent NSAIAs is feasible. Moreover, these compounds are not related to arachidonate metabolites.
Institute of Ocular Pharmacology, Texas A&M University, College of Medicine, College Station.
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Okawara
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000494:pharmacology*; D003459:Crystallins; D004731:Endotoxins; D005260:Female; D019793:Fluorescein; D005452:Fluoresceins / Q000378:metabolism; D015590:Fluorophotometry; D007097:Imines / Q000138:chemical synthesis / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D007375:Interleukin-1 / Q000037:antagonists & inhibitors*; D008297:Male; D011239:Prednisolone / Q000494:pharmacology; D011724:Pyridazines / Q000138:chemical synthesis / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D013843:Thiazines / Q000138:chemical synthesis / Q000494:pharmacology; D014605:Uveitis / Q000139:chemically induced / Q000517:prevention & control*
C091705:2-anilino-3-phenyl-1,3-thiazine; D000894:Anti-Inflammatory Agents, Non-Steroidal; C091706:CK 103A; D003459:Crystallins; D004731:Endotoxins; D005452:Fluoresceins; D007097:Imines; D007375:Interleukin-1; D011724:Pyridazines; D013843:Thiazines; C091704:CK 17; D011239:Prednisolone; D019793:Fluorescein