Anti-inflammatory effect of proteinase inhibitors on carrageenin-induced inflammation in rats.
Proteinase inhibitors were evaluated for their anti-inflammatory actions on carrageenin-induced inflammation in rats. The development of granulation tissue and the exudate were markedly suppressed by a single injection of L-1-tosylamide-2-phenylethyl chloromethyl ketone (TPCK) into the carrageenin-air-pouch immediately after carrageenin injection, whereas a single injection of TPCK at 12 or 24 hr after carrageenin injection was less effective or slightly effective respectively. These results suggest that proteinase inhibitors exert their anti-inflammatory actions by interfering with the initial inflammatory reactions after carrageenin injection. When the wet weight of granulation tissue and the weight of exudate were measured on day 4 after the simultaneous injection of carrageenin and inhibitors, a single injection of serine- and thiol-proteinase inhibitors including TPCK, leupeptin, antipain, chymostatin and cystamine suppressed the development of granulation tissue, though EDTA and o-phenanthroline, metallo-proteinase inhibitors, were also effective at a high dose. Exudate was reduced by treatment with TPCK in a dose-dependent manner, while EDTA and o-phenanthroline were effective only at a high dose. On the other hand, the migration of polymorphonuclear leukocytes into the carrageenin-air-pouch (the inflammatory lesion) was markedly suppressed by TPCK and leupeptin, while a high dose of cystamine and o-phenanthroline was slightly effective, and antipain, chymostatin, pepstatin, elastatinal, EDTA, trans-1-aminomethylcyclohexane 4-carboxylic acid and aprotinin were without effect.
D000818:Animals; D002351:Carrageenan; D002465:Cell Movement / Q000187:drug effects; D003538:Cystamine / Q000494:pharmacology; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology*; D007976:Leupeptins / Q000494:pharmacology; D008297:Male; D009504:Neutrophils / Q000473:pathology; D010618:Phenanthrolines / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D014108:Tosylphenylalanyl Chloromethyl Ketone / Q000494:pharmacology
D007976:Leupeptins; D010618:Phenanthrolines; D011480:Protease Inhibitors; D014108:Tosylphenylalanyl Chloromethyl Ketone; D002351:Carrageenan; D003538:Cystamine; C025205:1,10-phenanthroline