Role of tumor necrosis factor and interleukin-1 in endotoxin-induced middle ear effusions.
In a rat model, we investigated the role of tumor necrosis factor (TNF) and interleukin-1 (IL-1) in endotoxin-induced middle ear effusions (MEEs). After the eustachian tube was obstructed, the middle ear was transtympanically injected with 35 microL of either 1) 1 mg/ mL lipopolysaccharide (LPS); 2) LPS and 100 micrograms TNF binding protein (TNFbp); 3) LPS and 1 microgram IL-1 receptor antagonist (IL-1ra); or 4) LPS, TNFbp, and IL-1ra. Every 2 hours, the fluid within the middle ear was collected, and the quantity of albumin in the fluid, an index of vascular leakage, was determined by enzyme-linked immunosorbent assay. After 6 hours, the middle ear was fixed for histologic analysis. The TNFbp significantly attenuated vascular extravasation into the middle ear. The IL-1ra did not significantly alter effusion development. These results indicate that TNF, but not IL-1, is a mediator of LPS-induced MEE. Therefore, TNFbp may represent a novel approach to the treatment of otitis media with effusion.
Ball
S S
SS
Dept of Surgery, University of North Carolina School of Medicine, Chapel Hill 27599-7070, USA.
Prazma
J
J
Dais
C G
CG
Triana
R J
RJ
Pillsbury
H C
HC
D000418:Albumins / Q000032:analysis; D000818:Animals; D002352:Carrier Proteins / Q000494:pharmacology; D004432:Ear, Middle / Q000473:pathology; D007375:Interleukin-1 / Q000502:physiology*; D008070:Lipopolysaccharides; D009092:Mucous Membrane / Q000473:pathology; D010034:Otitis Media with Effusion / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D011550:Pseudomonas aeruginosa; D051381:Rats; D017207:Rats, Sprague-Dawley; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D053319:Tumor Necrosis Factor Decoy Receptors; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D000418:Albumins; D002352:Carrier Proteins; D007375:Interleukin-1; D008070:Lipopolysaccharides; D017472:Receptors, Interleukin-1; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D053319:Tumor Necrosis Factor Decoy Receptors; D014409:Tumor Necrosis Factor-alpha; C069521:recombinant human tumor necrosis factor-binding protein-1