6-ketoprostaglandin-f1-alpha and Pneumococcal-Infections

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.

Topics: 6-Ketoprostaglandin F1 alpha; Acute Disease; Animals; Azepines; Biphenyl Compounds; Chinchilla; Dinoprostone; Ear, Middle; Fatty Acids, Nonesterified; Heptanoic Acids; Hydrolases; Leukotriene Antagonists; Leukotriene C4; Mucous Membrane; Otitis Media; Phospholipids; Platelet Activating Factor; Platelet Membrane Glycoproteins; Pneumococcal Infections; Propionates; Quinolines; Receptors, Cell Surface; Receptors, G-Protein-Coupled; Receptors, Thromboxane; Thromboxane B2; Triazoles

The concentrations of four arachidonic acid metabolites, prostaglandin E2, 6-keto-prostaglandin F1 alpha, leukotriene B4, and leukotriene C4, were measured in middle ear fluid of chinchillas 6 to 72 hours after middle ear inoculation of log-phase, heat-killed encapsulated Streptococcus pneumoniae organisms. Compared with saline-inoculated ears, significant increases in the mean concentrations of all four metabolites were observed in the pneumococcus-inoculated ears 24 hours after inoculation, but not after 6, 48, or 72 hours. Since pneumococcus inoculation caused an influx of inflammatory cells as early as 6 hours after inoculation, before the increase in arachidonate metabolites, the initial stimulus for inflammatory cell chemotaxis is probably not metabolic products of arachidonic acid such as leukotriene B4. These metabolites may, however, amplify the subsequent inflammatory response.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Arachidonic Acid; Arachidonic Acids; Chinchilla; Dinoprostone; Leukotriene B4; Otitis Media with Effusion; Pneumococcal Infections; SRS-A; Time Factors