Inhibition of inflammatory cell infiltration by bicyclic imidazoles, SK&F 86002 and SK&F 104493.
The mode of action of the dual inhibitors of eicosanoid metabolism, SK&F 86002 and SK&F 104493 was evaluated on inflammatory cell infiltration induced in mice by carrageenan, monosodium urate crystals, and arachidonic acid. The results were compared to those seen with standard antiinflammatory compounds. Inflammatory cell infiltration was inhibited by SK&F 86002. SK&F 104493, colchicine, and phenidone but not naproxen. In vivo, PMN infiltration induced by LTB4 was inhibited by colchicine but not by SK&F 86002, SK&F 104493, or phenidone treatment. Similarly, in vitro chemotaxis to LTB4 was not inhibited by SK&F 86002. The 5-lipoxygenase inhibitors, SK&F 86002, SK&F 104493, and phenidone inhibited LTB4 production in vivo as well as inflammatory cell infiltration induced by arachidonic acid. The data are consistent with the suggestion that the bicyclic imidazoles inhibit PMN infiltration by virtue of inhibition of LTB4 production.
Griswold
D E
DE
Smith Kline and French Laboratories, King of Prussia, Pennsylvania 19406.
Hoffstein
S
S
Marshall
P J
PJ
Webb
E F
EF
Hillegass
L
L
Bender
P E
PE
Hanna
N
N
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D003520:Cyclophosphamide / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis; D004427:Ear Diseases / Q000209:etiology / Q000473:pathology; D004487:Edema / Q000209:etiology / Q000473:pathology; D015777:Eicosanoids / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D007093:Imidazoles / Q000494:pharmacology*; D007249:Inflammation / Q000378:metabolism / Q000473:pathology*; D007975:Leukotriene B4 / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000502:physiology; D010538:Peritonitis / Q000473:pathology / Q000503:physiopathology; D011725:Pyridines / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015777:Eicosanoids; D007093:Imidazoles; D011725:Pyridines; D013844:Thiazoles; C062693:2-(4-methoxyphenyl)-3-(4-pyridyl)-6,7-dihydro-(5H)-pyrrolo(1,2-a)imidazole; D007975:Leukotriene B4; D003520:Cyclophosphamide; C052026:6-(4-fluorophenyl)-2,3-dihydro-5-(4-pyridinyl)imidazo(2,1-b)thiazole; D015232:Dinoprostone