leukotriene-b4 and Otitis-Media-with-Effusion

Two potent mediators of acute inflammation, histamine and leukotriene B4 (LTB4), have been shown to play important roles in the pathogenesis and clinical course of acute otitis media (AOM) in children. The purpose of this study was to evaluate the ability of adjuvant drugs, antihistamine and corticosteroid, in reduction of the levels of histamine and LTB4 in the middle ear and their ability to improve outcomes of AOM.. Eighty children with AOM (aged 3 months to 6 years) were enrolled in a prospective, randomized, double-blind, placebo controlled study. All children received one dose of intramuscular ceftriaxone and were randomly assigned to receive either chlorpheniramine maleate (0.35 mg/kg per day) and/or prednisolone (2 mg/kg per day) or placebos three times a day for 5 days. Tympanocentesis was performed at enrollment and after 5 days of adjuvant drug treatment. MEFs were collected for bacterial and viral studies and histamine and LTB4 levels. The subjects were followed for the duration of middle ear effusion or up to 3 months.. Histamine or LTB4 levels in the MEF after 5 days of treatment were not significantly reduced by adjuvant drug treatment. However, subjects receiving corticosteroid had a lower rate of treatment failure during the first 2 weeks and shorter duration of middle ear effusion.. Five day of antihistamine or corticosteroid treatment does not reduce the levels of histamine or leukotriene B4 in the MEF of children with AOM. Positive clinical outcomes of AOM cases associated with corticosteroid treatment needs to be confirmed in a larger clinical trial of children with intact tympanic membranes, who do not receive tympanocentesis.

Topics: Acute Disease; Anti-Bacterial Agents; Anti-Inflammatory Agents; Ceftriaxone; Child; Child, Preschool; Chlorpheniramine; Double-Blind Method; Drug Therapy, Combination; Ear, Middle; Female; Histamine; Histamine H1 Antagonists; Humans; Infant; Leukotriene B4; Male; Otitis Media with Effusion; Prednisolone; Prospective Studies

Leukotrienes B4, C4 (LTB4, LTC4) and prostaglandin E2 (PGE2) are arachidonic acid metabolites which are released from various types of cells, and are considered to be the mediators of inflammation because of their potent vascular permeability increasing activity (LTC4 and PGE2) and chemotactic activity (LTB4). In this study, to evaluate the involvement of arachidonic acid metabolites in otitis media with effusion, we measured the LTB4, LTC4 and PGE2 in rat middle ear effusion (MEE) by radioimmunoassay (RIA). SD rats weighing about 200g were used. The animals were divided into two groups, and lipopolysaccaride (LPS) or concanavalin A (ConA) was injected into the right middle ear cavity through the tympanic membrane. The left middle ear cavities were injected with 200 microliters of phosphate balanced buffered saline (PBS) and used as controls. After stimulation, middle ear effusion and accumulation of inflammatory cells such as neutrophils, macrophages, and lymphocytes was observed in the middle ear cavity. In contrast, no inflammatory cells were observed in the control ears. Proteins exudated into the middle ear cavity after LPS or ConA injection. The protein content increased up to 3 days, and then decreased. Substantial amounts of LTs and PG were detected in experimental rat OME, although hardly and LTs or PG was detected in the control ears or serum. LTs levels increased up to 7 days, and then decreased. PGE2 levels increased up to 3 days, and decreased thereafter. Dexamethasone effectively suppressed protein exudation, cell accumulation and production of arachidonic acid metabolites in the middle ear.

Topics: Animals; Dinoprostone; Leukotriene B4; Leukotriene C4; Male; Otitis Media with Effusion; Rats; Rats, Sprague-Dawley

Middle ear effusions (MEEs) from 78 children (98 ears) with otitis media were examined for products of arachidonic acid (AA) metabolism, including leukotrienes B4, C4, D4, and E4 and prostaglandins D2 and E2, by high-performance liquid chromatography. Leukotrienes B4 and D4 were recovered most frequently: 59% and 54%, respectively. Leukotriene B4 was found in highest concentration, 1.29 +/- 3.46 ng/0.1 mL. The concentrations of leukotrienes B4 (p less than .03), (4 (p less than .01), and E4 (p less than .02) were significantly higher in culture-positive than in culture-negative MEEs. Neither the concentration nor the type of AA metabolite correlated with bacterial species isolated, chronicity of effusion, age of subject, or consistency of MEE. These data suggest that the AA metabolites are synthesized relatively frequently during otitis media of childhood. Leukotriene B4 is the most frequently detected AA metabolite in MEEs and is highly associated with the presence of viable bacteria.

Topics: Arachidonic Acid; Arachidonic Acids; Bacteria; Child, Preschool; Chromatography, High Pressure Liquid; Dinoprostone; Female; Humans; Infant; Infant, Newborn; Leukotriene B4; Leukotriene E4; Longitudinal Studies; Male; Otitis Media with Effusion; Prostaglandin D2; SRS-A

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

Although previous studies have shown that prostaglandins (PGs), leukotrienes (LTs), and other arachidonic acid (AA) metabolites play an important role in the pathogenesis of otitis media with effusion (OME), the exact role of each AA metabolite in OME is still unknown. The purpose of this study was to examine the effect of several individual AA metabolites alone or in combination and AA itself on experimental otitis media in chinchillas. Normal chinchillas were inoculated daily with normal saline, PGE2, LTC4, LTC4 + PGE2, and AA through the superior bullae over 7 days. Animals were followed by otoscopy and tympanometry, samples of middle ear effusion were collected for biochemical assay, and temporal bones were processed for histopathology. The highest number of ears that developed OME was in the group inoculated with PGE2 + LTC4. The degree of inflammatory change was more pronounced in groups injected with LTC4 than any other group. The findings of this study suggest that eicosanoids PGE2, LTC4, and AA alone or in combination inoculated into the middle ear can induce OME.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Arachidonic Acid; Arachidonic Acids; Chinchilla; Dinoprost; Dinoprostone; Hydroxyeicosatetraenoic Acids; Leukocytes; Leukotriene B4; Mucous Membrane; Muramidase; Otitis Media with Effusion; Prostaglandin D2; SRS-A

Among the various inflammatory mediators of otitis media (OM), metabolites of arachidonic acid (AA) such as prostaglandins (PGs) and leukotrienes (LTs) appear to play an important role in the pathogenesis of otitis media. In an effort to investigate the role of AA metabolites on the pathogenesis of otitis media, concentrations of AA metabolites were measured in middle ear effusion (MEE) from human and paralleling animal models of otitis media and the effects of inhibitors of AA metabolism, antibiotics, and tympanostomy tube (TT) on the outcome of animal models of OM were studied. Concentrations of AA metabolites in MEE were higher in the younger age group. Levels of PGE2 and LTB4 in MEE seem to represent the degree of inflammation of OM best. Lipoxygenase products seem to be associated with the mucoid type of MEE. In the study of animal models of OM, combined models and ears with TT showed more inflammation than single models and ears without TT. Study of the therapeutic use of inhibitors of AA metabolism, penicillin, and TT showed that lipoxygenase products may be more important in the pathogenesis of OM than the cyclo-oxygenase products, and that the use of a combination of penicillin and corticosteroid produces the best results. It is clear from these studies that arachidonic acid metabolites are important inflammatory mediators in the pathogenesis of otitis media.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Arachidonic Acids; Chinchilla; Dinoprostone; Disease Models, Animal; Humans; Hydrocortisone; Hydroxyeicosatetraenoic Acids; Ibuprofen; Leukotriene B4; Middle Ear Ventilation; Otitis Media with Effusion; Penicillin G; Prostaglandins; Prostaglandins E; SRS-A; Temporal Bone; Thromboxane B2