15-hydroxy-5-8-11-13-eicosatetraenoic-acid and Colitis

This study was performed to determine whether 15-HETE, which is the major metabolite of arachidonic acid (AA) in inflamed and normal human colonic tissue, has pro- or anti-inflammatory properties. To investigate these effects, 15-HETE (100 micrograms/kg/day) was administered rectally to mice with colitis induced by dextran sodium sulphate (DSS). Colons were removed and examined macroscopically and histologically and specimens were incubated with [14C]-AA and stimulated with A23187. Exogenous eicosanoids were separated by HPLC; the endogenously formed mediators were measured by radioimmunoassay. DSS produced a marked diffuse inflammatory response in the colon, associated with a raised inflammation score (mean 7.6 vs. < 0.5) and a significant increase in endogenously formed metabolites PGE2, LTB4 and 12-HETE. 15-HETE treatment resulted in a slight decrease in inflammation score (6.4 vs. 7.6) and a slight, but not significant, decrease in endogenous LTB4.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Colitis; Dextran Sulfate; Eicosanoids; Female; Hydroxyeicosatetraenoic Acids; Mice; Mice, Inbred BALB C