title: Effects of 16,16-dimethyl prostaglandin E2 and indomethacin on leukotriene B4 and inflammation in rabbit colitis.
abstract: The role of increased prostaglandin production and the effects of exogenous prostaglandins on inflammation of colitis are not established. We administered intramuscular 16,16-dimethyl prostaglandin E2 (DiM-PGE2) and indomethacin to rabbits with formalin immune-complex colitis and measured leukotriene B4 (LTB4), prostaglandin E2 (PGE2) and severity of inflammation. DiM-PGE2 (100 micrograms/kg/BID) reduced LTB4 production (from 401 +/- 108 to 216 +/- 58 pg/ml) and infiltration of neutrophils, mucosal necrosis, inflammatory exudate and edema (all P less than 0.05). Other studies determined that parenteral DiM-PGE2 did not reduce the initial chemical damage induced by formalin, suggesting that cytoprotection of chemical insult was not the mechanism of suppressed inflammation in the immune colitis model. Indomethacin (10 mg/kg/d) reduced endogenous PGE2 by 80%, but did not reduce leukotriene production or inflammation. Exogenous prostaglandins cause a dose-dependent suppression of inflammation in experimental colitis, by a mechanism other than cytoprotection of chemical-induced mucosal injury.
authors.affiliation: Department of Medicine, Harbor-UCLA Medical Center 90509.
authors.forename: R
authors.initials: R
authors.lastname: Schumert
authors.forename: C C
authors.initials: CC
authors.lastname: Nast
authors.forename: F
authors.initials: F
authors.lastname: Cominelli
authors.forename: R D
authors.initials: RD
authors.lastname: Zipser
mesh_terms: D000818:Animals; D003092:Colitis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003106:Colon / Q000473:pathology; D015232:Dinoprostone / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D007213:Indomethacin / Q000627:therapeutic use*; D007975:Leukotriene B4 / Q000378:metabolism*; D008297:Male; D009336:Necrosis; D011459:Prostaglandins E, Synthetic / Q000627:therapeutic use*; D011817:Rabbits
chemical_list: D011459:Prostaglandins E, Synthetic; D007975:Leukotriene B4; C017244:16,16-dimethylprostaglandin E; D015232:Dinoprostone; D007213:Indomethacin