interleukin-8 and Otitis-Media--Suppurative

Otitis media is characterized as an ongoing inflammation with accumulation of an effusion in the middle ear cleft. The molecular mechanisms underlying the pathogenesis, particularly the inflammatory response, remain largely unknown. We hypothesize that aspiration of gastric contents into the nasopharynx may be responsible for the initiation of the inflammatory process or aggravate a preexisting condition.. To investigate the correlation of gastric pepsin A with inflammatory cytokines, bacterial infection, and clinical outcomes.. Prospective study of 129 pediatric patients undergoing myringotomy with tube placement for otitis media at a tertiary care pediatric hospital.. Ear samples were tested for pepsin A; cytokines interleukin (IL)-6, IL-8, and tumor necrosis factor; and bacterial culture inoculation. Data were analyzed by descriptive statistics and regression analysis to identify risk factors for the presence of pepsin A and to correlate pepsin A levels with cytokine levels, infection status, and clinical outcomes.. Of the 129 patients, 199 ear samples were obtained; 82 samples (41%) and 64 patients (50%) were positive for pepsin A as measured by immunoassay. Pepsin A positivity correlated with age younger than 3.0 years (mean [SD], 2.3 [2.1] years in the positive group vs 3.3 [3.0] years in the negative group) and with all 3 cytokine levels (mean [SD] tumor necrosis factor, 29.5 [45.9] pg/mL in the positive group vs 13.2 [21.6] pg/mL in the negative group; IL-6, 6791.7 [9389.1] pg/mL in the positive group vs 2849.9 [4066.3] pg/mL in the negative group; and IL-8, 6828.2 [8122.3] pg/mL in the positive group vs 2925.1 [3364.5] pg/mL in the negative group [all P < .05]); however, logistic regression analysis showed that only IL-8 (odds ratio, 3.96; 95% CI, 1.3-12.0; P = .02) and age (odds ratio, 3.83; 95% CI, 1.2-12.7; P = .03) were significant independent variables. No statistically significant association was found with other parameters. Multiple linear regressions revealed that the levels of pepsin A were correlated with IL-8 levels (R2 = 0.248; P < .001) and the need for second or third tubes 6 to 12 months after the first (R2 = 0.102; P = .006). The presence of pepsin A in the middle ear was not associated with increased bacterial infection. Interleukin 8 was independent and significantly associated with both pepsin A levels and bacterial infection (R2 = 0.144 and 0.263, respectively; P = .001 for both).. Extraesophageal reflux as indicated by the presence of pepsin A is closely involved in the middle ear inflammatory process and may worsen the disease in some children; however, a proof of cause and effect between extraesophageal reflux and middle ear inflammation requires further investigation.

Topics: Child; Child, Preschool; Female; Gastroesophageal Reflux; Haemophilus influenzae; Humans; Infant; Interleukin-6; Interleukin-8; Male; Middle Ear Ventilation; Moraxella catarrhalis; Otitis Media with Effusion; Otitis Media, Suppurative; Pepsin A; Prospective Studies; Risk Factors; Streptococcus pneumoniae; Tumor Necrosis Factor-alpha

Interleukin-8 (IL-8), a potent neutrophilic chemoattractant and inflammatory cytokine, is present in middle ear effusions (MEEs) of children with otitis media and is thought to be responsible for the accumulation of neutrophils in MEEs. We hypothesized that IL-8 concentration predicts the total number and proportion of neutrophils in MEEs. IL-8 concentration and total and differential cell counts were measured in MEEs of children undergoing tympanostomy tube placement for otitis media. IL-8 was present in 80 (98%) of 82 effusions. The mean +/- SEM value for IL-8 was 7342 +/- 847 pg/mL. The mean +/- SEM count and percentage of neutrophils were 1.34 x 10(6) +/- 3.44 x 10(5) and 70.6 +/- 3.1%, respectively. IL-8 concentrations correlated positively with the total number (r = +0.30; P = 0.02) and percentage of neutrophils (r = +0.32; P = 0.01) in the effusion. Additionally, purulent effusions had greater IL-8 concentrations (P = 0.003) and greater neutrophil count (P = 0.03) than mucoid or serous effusions. We conclude that IL-8 is consistently present in MEEs of children and IL-8 concentration predicts the total number and proportion of neutrophils. Furthermore, IL-8 concentration and the total number of neutrophils correlate positively with the type of effusion. These results support the hypothesis that IL-8 recruits neutrophils to the middle ear in MEEs.

Topics: Adolescent; Analysis of Variance; Cell Count; Chemotaxis, Leukocyte; Child; Child, Preschool; Enzyme-Linked Immunosorbent Assay; Female; Forecasting; Humans; Immunohistochemistry; Infant; Interleukin-8; Leukocyte Count; Lymphocyte Count; Macrophages; Male; Middle Ear Ventilation; Monocytes; Mucus; Neutrophils; Otitis Media with Effusion; Otitis Media, Suppurative