Cytokine expression in otitis media with effusion. Tumor necrosis factor soluble receptor.
BACKGROUND
A variety of cytokines, such as interleukin 1 and tumor necrosis factor (TNF), appear to play a key role in the initiation and maintenance of the inflammatory response in a variety of diseases, including chronic otitis media with effusion (COME). Recently, cytokine inhibitors have been isolated and are presumed to regulate the proinflammatory effects of these cytokines. This has lead us to hypothesize that the chronic inflammation seen in COME is the result of an imbalance in the ratio of proinflammatory cytokines and inhibitors that favors the proinflammatory cytokines.


METHODS
Middle ear effusions were evaluated for the cytokine TNF-alpha and the inhibitor TNF soluble receptor (TNFsolR) using a combination of enzyme-linked immunosorbent assays and radioactive immunoassays. We determined the presence and quantified the amounts of TNF-alpha and TNFsolR and correlated this result with clinical parameters in patients with COME.


METHODS
University hospital.


METHODS
To test this hypothesis, 35 middle ear effusions were obtained from 29 children aged 2 to 102 months (mean, 39.6 months) undergoing tympanostomy tube insertion for COME.


RESULTS
Children were followed up for at least 12 months postoperatively and the number of subsequent episodes of otitis media correlated with cytokine levels.


RESULTS
The TNF-alpha and TNFsolR were present in 83% and 91% of effusions, respectively. The TNF-alpha mean (+/-SEM) cytokine values were 110.6 +/- 32.1 pg/mg of total protein, and 12886 +/- 3108 pg/mg total protein for TNFsolR. Analysis of correlations in a univariate model revealed a statistically significant relationship for TNF-alpha correlated with TNFsolR (R2 = 0.463; P < .001). The TNF-alpha levels were significantly lower for children with multiple tube insertions (P = .02). Higher levels of TNF-alpha were noted in those children who subsequently developed episodes of otitis media after tube placement (P = .02). The ratio of TNF-alpha to TNFsolR, the mean (+/-SEM) inhibitor index was 430 +/- 220 U.


CONCLUSIONS
Our data support the hypothesis that cytokines and their inhibitors are present in a large number of middle ear effusions and in part are likely important in the regulation of inflammatory processes in COME.
Maxwell
K
K
Department of Surgery, University of Connecticut Health Center, Farmington, USA.
Leonard
G
G
Kreutzer
D L
DL
D000704:Analysis of Variance; D002675:Child, Preschool; D002908:Chronic Disease; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D015870:Gene Expression; D006801:Humans; D007223:Infant; D007375:Interleukin-1 / Q000032:analysis / Q000235:genetics; D008297:Male; D008876:Middle Ear Ventilation; D015999:Multivariate Analysis; D009363:Neoplasm Proteins / Q000032:analysis* / Q000235:genetics; D010034:Otitis Media with Effusion / Q000378:metabolism*; D011506:Proteins / Q000032:analysis; D011863:Radioimmunoassay; D011956:Receptors, Cell Surface / Q000032:analysis* / Q000235:genetics; D047889:Receptors, Tumor Necrosis Factor, Type II; D012008:Recurrence; D012086:Reoperation; D053319:Tumor Necrosis Factor Decoy Receptors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis* / Q000037:antagonists & inhibitors / Q000235:genetics
D007375:Interleukin-1; D009363:Neoplasm Proteins; D011506:Proteins; D011956:Receptors, Cell Surface; D047889:Receptors, Tumor Necrosis Factor, Type II; D053319:Tumor Necrosis Factor Decoy Receptors; D014409:Tumor Necrosis Factor-alpha