Enhanced formation of sulfidopeptide-leukotrienes in ulcerative colitis and Crohn's disease: inhibition by sulfasalazine and 5-aminosalicylic acid.
Release of sulfidopeptide (SP)-leukotrienes (LT) in vitro from normal human colonic mucosa and from mucosal tissue obtained from patients with Crohn's disease (CD) and ulcerative colitis (UC) was investigated. It was found that inflamed mucosal tissue released significantly more SP-LT than normal colonic mucosa both under control conditions and after addition of calcium ionophore A23187. These results indicate the presence of endogenous stimuli as well as an increased responsiveness to an exogenous stimulus of LT formation in the inflamed mucosa. Sulfasalazine (SASP), a drug used in inflammatory bowel diseases, and its active metabolite 5-aminosalicylic acid (5-ASA) were found to inhibit colonic mucosal SP-LT formation, while only 5-ASA inhibited simultaneously synthesis of another arachidonic acid-derived inflammatory mediator, prostaglandin (PG) E2. The results suggest that SP-LT might be important mediators of inflammation in CD and UC.
D000636:Aminosalicylic Acids / Q000494:pharmacology*; D003093:Colitis, Ulcerative / Q000378:metabolism*; D003424:Crohn Disease / Q000378:metabolism*; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D017999:Leukotriene E4; D019804:Mesalamine; D012007:Rectum / Q000378:metabolism; D012016:Reference Values; D013189:SRS-A / Q000031:analogs & derivatives* / Q000097:blood*; D012460:Sulfasalazine / Q000494:pharmacology*
D000636:Aminosalicylic Acids; D013189:SRS-A; D012460:Sulfasalazine; D019804:Mesalamine; D017999:Leukotriene E4