In vivo effects of orally administered prednisolone on prostaglandin and leucotriene production in ulcerative colitis.
It has been proposed that anti-inflammatory actions of corticosteroids rely on promotion of a natural peptide phospholipase A2 inhibitor, lipocortin, but in vivo effects on arachidonic acid metabolism have not been shown. Equilibrium dialysis of the rectum in patients with ulcerative colitis was used to determine whether cyclooxygenase and lipoxygenase products released from the inflamed rectal mucosa could be differentially inhibited by systemic treatment with prednisolone and indomethacin, respectively. In 10 patients with severe disease luminal concentrations of prostaglandin E2, prostaglandin F2 alpha, and leucotriene B4 were markedly raised (p less than 0.05) on comparison with 10 healthy controls, and they decreased significantly (p less than 0.05) within 72 hours after administration of prednisolone 1.5 mg/kg/day orally. In contrast prostaglandin, but not leucotriene B4 concentrations decreased (p less than 0.05) within 72 hours after administration of indomethacin 150 mg/day in another 10 patients with distal disease. These prompt reductions in concentrations of arachidonic acid metabolites more likely are caused by direct drug actions, rather than being secondary to decreased tissue damage. The data accord with the theory explaining anti-inflammatory effects of corticosteroids through lipocortin activity and support the belief that leucotrienes are more important than prostaglandins as mediators of inflammation in ulcerative colitis.
Lauritsen
K
K
Department of Medical Gastroenterology, Odense University Hospital, Denmark.
Laursen
L S
LS
Bukhave
K
K
Rask-Madsen
J
J
D000328:Adult; D000368:Aged; D003093:Colitis, Ulcerative / Q000188:drug therapy / Q000378:metabolism*; D015237:Dinoprost; D015232:Dinoprostone; D005260:Female; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000378:metabolism; D007975:Leukotriene B4 / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D011239:Prednisolone / Q000494:pharmacology*; D011453:Prostaglandins / Q000096:biosynthesis*; D011458:Prostaglandins E / Q000096:biosynthesis; D011460:Prostaglandins F / Q000096:biosynthesis; D012007:Rectum / Q000378:metabolism
D011453:Prostaglandins; D011458:Prostaglandins E; D011460:Prostaglandins F; D007975:Leukotriene B4; D011239:Prednisolone; D015237:Dinoprost; D015232:Dinoprostone; D007213:Indomethacin