Release of 15-hydroxy-5,8,11,13-eicosatetraenoic acid and cysteinyl-leukotrienes in carrageenin-induced inflammation: effect of non-steroidal anti-inflammatory drugs.
Inflammatory exudates obtained in rats after subcutaneous implantation of carrageenin-soaked sponges were found to contain relatively large amounts of 15-hydroxy-5,8,11, 13-eicosatetraenoic acid (15-HETE) and smaller amounts of cysteinyl-leukotrienes (LT) in addition to LTB4, thromboxane (TX) B2 and prostaglandin (PG)E2. Concentrations of 15-HETE and cysteinyl-LT were high 5 hours after sponge implantation and decreased significantly within 24 hours. This time-course, which is similar to that of TXB2, but differs from that of PGE2, suggests migrating leukocytes as a major source of 15-HETE and cysteinyl-LT. Aspirin, sodium salicylate, dipyrone (100 mg/kg each) and indomethacin (2 and 20 mg/kg) decrease the concentrations of cyclooxygenase products of arachidonate metabolism, but did not significantly affect levels of 15-HETE. Cysteinyl-LT were increased by 20 mg/kg indomethacin, but remained unaffected by 2 mg/kg indomethacin and by the other non-steroidal anti-inflammatory drugs (NSAID) tested. 15-HETE and cysteinyl-LT could play a mediator role in inflammation. In addition, they could modulate the release and effects of other inflammatory mediators.
Peskar
B M
BM
Department of Experimental Clinical Medicine, Ruhr-University of Bochum, FRG.
Trautmann
M
M
Nowak
P
P
Peskar
B A
BA
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002351:Carrageenan; D002851:Chromatography, High Pressure Liquid; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism*; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism*; D007975:Leukotriene B4 / Q000378:metabolism; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008297:Male; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D013189:SRS-A / Q000378:metabolism; D013929:Thromboxane B2 / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D006893:Hydroxyeicosatetraenoic Acids; D016859:Lipoxygenase Inhibitors; D013189:SRS-A; D007975:Leukotriene B4; D013929:Thromboxane B2; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; D002351:Carrageenan; D015232:Dinoprostone