title: Expression of acute otitis media after receptor blockade of platelet activating factor, thromboxane, and leukotrienes in the chinchilla.
abstract: To determine the role of inflammatory products of phospholipid metabolism in acute otitis media (AOM), we infected 128 chinchillas with Streptococcus pneumoniae and randomly assigned them to one of four equal-sized treatment groups receiving intramuscular ampicillin sodium (control) or intramuscular ampicillin plus receptor blockers of platelet activating factor (WEB 2086, 5 mg/d orally), of leukotriene (MK 571, 0.5 mg/d orally), or of thromboxaneA2 (GR 32191B, 5 mg/d orally). All treatments were begun on day 2 postinoculation and continued for 10 days. On days 3, 6, 9, and 12, 8 animals from each group were sacrificed. Effusions were recovered for biochemical assay, and the right middle ears were prepared for histologic study. Differences among groups in the number of ears with effusion or in effusion volume were not statistically significant. In comparison to the control group, mucosal thickness and the number of ears with histopathologic signs of inflammation were significantly less in the GR and WEB treatment groups, but not the MK group. Also, effusion concentrations of free fatty acids, protease, and hydrolytic enzymes were significantly less in those groups. These results show that the addition of a receptor blocker for either platelet activating factor and/or thromboxane to ampicillin in the treatment of AOM reduces mucosal inflammation and decreases the production of other inflammatory chemicals. The failure of a receptor blocker of leukotrienes to moderate disease expression suggests either a less important role for these chemicals in AOM or an insufficient bioavailability of the specific MK 571 inhibitor. These results confirm that platelet activating factor and thromboxane are active mediators of inflammation in AOM.
authors.affiliation: Department of Pathology, University of Pittsburgh School of Medicine, Pennsylvania, USA.
authors.forename: W F
authors.initials: WF
authors.lastname: Diven
authors.forename: G J
authors.initials: GJ
authors.lastname: Burckart
authors.forename: C M
authors.initials: CM
authors.lastname: Alper
authors.forename: R
authors.initials: R
authors.lastname: Jaffe
authors.forename: R W
authors.initials: RW
authors.lastname: Evans
authors.forename: W J
authors.initials: WJ
authors.lastname: Doyle
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000208:Acute Disease; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D002682:Chinchilla; D015232:Dinoprostone / Q000378:metabolism; D004432:Ear, Middle / Q000473:pathology; D005230:Fatty Acids, Nonesterified / Q000032:analysis; D006538:Heptanoic Acids / Q000494:pharmacology; D006867:Hydrolases / Q000378:metabolism; D020024:Leukotriene Antagonists; D017997:Leukotriene C4 / Q000378:metabolism; D009092:Mucous Membrane / Q000473:pathology; D010033:Otitis Media / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D010743:Phospholipids / Q000378:metabolism; D010972:Platelet Activating Factor / Q000378:metabolism; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors*; D011008:Pneumococcal Infections / Q000378:metabolism; D011422:Propionates / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors*; D013929:Thromboxane B2 / Q000378:metabolism; D014230:Triazoles / Q000494:pharmacology
chemical_list: D001381:Azepines; D001713:Biphenyl Compounds; D005230:Fatty Acids, Nonesterified; D006538:Heptanoic Acids; D020024:Leukotriene Antagonists; D010743:Phospholipids; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011422:Propionates; D011804:Quinolines; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D017482:Receptors, Thromboxane; D014230:Triazoles; C039351:platelet activating factor receptor; C052518:WEB 2086; D017997:Leukotriene C4; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; C059141:verlukast; D006867:Hydrolases; C060013:vapiprost; D015232:Dinoprostone