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Tumor Necrosis Factor Soluble Receptor

Kenneth Maxwell, MD; Gerald Leonard, MD; Donald L. Kreutzer, PhD

Arch Otolaryngol Head Neck Surg. 1997;123(9):984-988.

Abstract
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.

Design
Middle ear effusions were evaluated for the cytokine TNF- 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- and TNFsolR and correlated this result with Clinical parameters in patients with COME.

Setting
University hospital.

Patients
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.

Outcome
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- and TNFsolR were present in 83% and 91% of effusions, respectively. The TNF- mean (±SEM) cytokine values were 110.6±32.1 pg/mg of total protein, and 12 886±3108 pg/mg total protein for TNFsolR. Analysis of correlations in a univariate model revealed a statistically significant relationship for TNF- correlated with TNFsolR (R²=0.463; P<.001). The TNF- levels were significantly lower for children with multiple tube insertions (P=.02). Higher levels of TNF- were noted in those children who subsequently developed episodes of otitis media after tube placement (P=.02). The ratio of TNF- 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.

Arch Otolaryngol Head Neck Surg. 1997;123:984-988

Author Affiliations
From the Departments of Surgery and Surgical Research Center (Drs Maxwell, Leonard, and Kreutzer) and Pathology (Dr Kreutzer), University of Connecticut Health Center, Farmington.

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