thromboxane-b2 and Otitis-Media

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

Bone resorption is a common finding in chronic otitis media with or without cholesteatoma. The etiology of bone resorption in chronic otitis media is still not clear. Bone-resorbing activity of prostaglandins (PGs) has been well known. PGE-like material has been detected in granulation tissue. However, there have been no reports on the comprehensive study of PGs in cholesteatomas or granulation tissue. The purpose of this study is to show that PGs are synthesized in the middle ear tissue and to report concentrations of PGs in cholesteatomas and granulation tissue. Samples of cholesteatoma and granulation tissues were obtained at the time of tympanomastoidectomies. Prostaglandin synthesizing activity was determined by incubating tissue with labeled arachidonic acid (precursor of PGs) and radiochromatography. Levels of PGs were determined by radioimmunoassay. Arachidonic acid metabolites produced in cholesteatoma and granulation tissue included PGE2; 6-keto-PGF1 alpha; PGF2 alpha; PGD2; and 5-, 12-, and 15-hydroxy-eicosatetraenoic acid (HETE). Levels of PGE2 were 2.6 times higher in cholesteatoma (106.8 +/- 46 ng/g) than in granulation tissue (41.0 +/- 14.3 ng/g). Levels of 6-keto-PGF1 alpha were two times higher in granulation tissue (89.0 +/- 27.0 ng/g) than in cholesteatoma. Levels of thromboxane B2 were two times higher in cholesteatoma than in granulation tissue. The results of this study demonstrate that cholesteatoma and granulation tissues actively synthesize PGs and contain high concentrations of them. Since PGs are locally active hormones, the presence of PGs indicates an active role for PGs in the pathogenesis of chronic otitis media with bone resorption.

Topics: 6-Ketoprostaglandin F1 alpha; Bone Resorption; Cholesteatoma; Chronic Disease; Dinoprost; Dinoprostone; Granulation Tissue; Humans; Hydroxyeicosatetraenoic Acids; Otitis Media; Prostaglandins; Thromboxane B2