15-Hydroxy-eicosatetraenoic acid has minor anti-inflammatory properties in 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.
van Dijk
A P
AP
Dept. of Pharmacology, Erasmus University, Rotterdam, The Netherlands.
McCafferty
D M
DM
Wilson
J H
JH
Zijlstra
F J
FJ
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D016264:Dextran Sulfate; D015777:Eicosanoids / Q000096:biosynthesis; D005260:Female; D006893:Hydroxyeicosatetraenoic Acids / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015777:Eicosanoids; D006893:Hydroxyeicosatetraenoic Acids; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; D016264:Dextran Sulfate