Sulfasalazine inhibits the synthesis of chemotactic lipids by neutrophils.
Neutrophils metabolize arachidonic acid through the liposygenase pathway to 5-hydroxy-6,8,11,14-eicosatetrenoic acid (5-HETE) and 5,12-dihydroxy-6,8,10,14-eicosatraenoic acid (5,12 diHETE). 5-HETE and 5,12diHETE are potent chemotactic agents and are thought to have important roles in the inflammatory response. In this study we demonstrate the sulfasalazine, at concentrations found in the stool of patients being treated for ulcerative colitis, blocks the synthesis of both 5-HETE and 5,12 diHETE by human neutrophils. A sulfasalazine metabolite, 5-aminosalicylate, also blocks the synthesis of 5,12 diHETE.
D000636:Aminosalicylic Acids / Q000494:pharmacology; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids; D007213:Indomethacin / Q000494:pharmacology; D007975:Leukotriene B4; D019804:Mesalamine; D009504:Neutrophils / Q000378:metabolism*; D012460:Sulfasalazine / Q000494:pharmacology*
D000636:Aminosalicylic Acids; D001095:Arachidonic Acids; D006893:Hydroxyeicosatetraenoic Acids; D007975:Leukotriene B4; D016718:Arachidonic Acid; D000001:Calcimycin; D012460:Sulfasalazine; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; D019804:Mesalamine; D007213:Indomethacin