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

Eicosanoids were measured in colonic biopsies from eleven patients with active ulcerative colitis and from thirteen controls. Eicosanoid formation was measured after the addition of arachidonic acid and stimulation with calcium ionophore A23187. The 15-lipoxygenase derivative 15-hydroxy-eicosatetraenoic acid (15-HETE) was the predominant product formed in all biopsies. The amount of 15-HETE formed was dependent on the site of biopsy and decreased in the controls in biopsies taken in an aboral direction in the colon. The formation of 15-HETE and that of prostaglandin E2 (PGE2) and PGF2 alpha was proportional to the histologically obtained inflammation score. The role of 15-H(P)ETE as a mediator in ulcerative colitis should, therefore, be considered in addition to the effects of known modulators such as leukotriene B4 (LTB4) and PGE2.

Topics: Adult; Arachidonic Acid; Biopsy; Calcimycin; Colitis, Ulcerative; Colon; Eicosanoids; Female; Humans; Hydroxyeicosatetraenoic Acids; Intestinal Mucosa; Male; Middle Aged

The synthesis of 14C labelled arachidonic acid metabolites was measured in colonic tissues obtained from mice, rats, guinea pigs, rabbits, piglets and in colonic biopsies from humans during colonoscopy. The main eicosanoids formed after stimulation with calcium ionophore A23187 were: in humans, 15-hydroxy-eicosatetraenoic acid (15-HETE); in mice, 12-HETE; in rats, 12-HETE, 12-hydroxy-5,8,10-heptadecatrienoic acid (HHT) and 6-keto-prostaglandin F1 alpha (6kPGF1 alpha); in guinea pigs, PGD2; in rabbits, 6kPGF1 alpha, PGE2 and 15-HETE; and in pigs PGE2 and 12-HETE. In inflamed 15-HETE production was increased in man, HHT and 12-HETE production in rats and overall eicosanoid production in mice.

Topics: 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; 6-Ketoprostaglandin F1 alpha; Animals; Calcimycin; Colitis, Ulcerative; Colon; Dinoprostone; Eicosanoids; Fatty Acids, Unsaturated; Guinea Pigs; Humans; Hydroxyeicosatetraenoic Acids; Intestinal Mucosa; Mice; Mice, Inbred BALB C; Prostaglandin D2; Rabbits; Rats; Rats, Wistar; Species Specificity

Prostaglandins, leukotrienes and mono-hydroxy acid products of arachidonic acid were measured in mucus of freshly recovered morning stools of a patient with an exacerbation of ulcerative proctocolitis. Eicosanoids in ether extracts were separated by high performance liquid chromatography and amounts determined by radioimmunoassay. Four hydroxy-eicosatetraenoic acids were detected, of which the most important one was identified as 15-hydroxy eicosatetraenoic acid (530 ng/g mucus). Leukotriene B4 was also present (21 ng/g mucus) and small amounts of immunoreactive leukotriene C4 (less than 0.8 ng/g mucus). The prostaglandins 6-keto-PGF1 alpha and PGE2 and thromboxane B2 were found in amounts of 3.7, 2.0 and 9.2 ng/g mucus, respectively.

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Colitis, Ulcerative; Eicosanoids; Feces; Humans; Hydroxyeicosatetraenoic Acids; Intestinal Mucosa; Leukotriene B4; Lipoxygenase Inhibitors; Male; Mucus; Proctitis