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 35μL of either 1) 1 mg/ mL lipopolysaccharide (LPS); 2) LPS and 100 μg TNF binding protein (TNFbp); 3) LPS and 1 μg 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.
GatesGA. Acute otitis media and otitis media with effusion. In: CummingsCWHarkerLA, eds. Otolaryngology-head and neck surgery. St Louis, Mo: Mosby-Year Book, 1993: 2802–22.
3.
DeMariaTFBriggsBRLimDJOkazakiN. Experimental otitis media with effusion following middle ear inoculation of nonviable H influenzae. Ann Otol Rhinol Laryngol1984; 93: 52–6.
4.
BernsteinJMPrainoMDNeterE. Detection of endotoxin in ear specimens from patients with chronic otitis media by means of the Limulus amebocyte lysate test. Can J Microbiol1980; 26: 546–8.
5.
DeMariaTFPriorRBBriggsBRLimDJBirckHG. Endotoxin in middle-ear effusions from patients with chronic otitis media with effusion. J Clin Microbiol1984; 20: 15–7.
6.
IinoYKanekoYTakasakaT. Endotoxin in middle ear effusions tested with Limulus assay. Acta Otolaryngol (Stockh)1985; 100: 42–50.
7.
NonomuraNMNakanoYSatohYFujiokaONiijimaHFujitaM. Otitis media with effusion following inoculation of Haemophilus influenzae type b endotoxin. Arch Otorhinolaryngol1986; 243: 31–5.
8.
OhashiYNakaiYIkeokaH. Functional disorder of eustachian tube in experimental otitis media with effusion following inoculation of bacterial endotoxin. Ann Otol Rhinol Laryngol1988; 97: 422–6.
9.
OhashiYNakaiYIkeokaHEsakiYKatoSKatoM. Experimental otitis media with effusion induced by lipopolysaccharide from Klebsiella pneumoniae: mucociliary pathology of the middle ear. Am J Otolaryngol1988; 9: 83–9.
10.
OhashiYNakaiYFuruyaH. Mucociliary disease of the middle ear during experimental otitis media with effusion induced by bacterial endotoxin. Ann Otol Rhinol Laryngol1989; 98: 479–84.
11.
OhashiYNakaiYEsakiYOhnoYSugiuraYOkamotoH. Experimental otitis media with effusion induced by lipopolysaccharide from Klebsiella pneumoniae: mucociliary pathology of the eustachian tube. Acta Otolaryngol [Suppl] (Stockh) 1991(suppl 486): 105–15.
BernsteinJMTsutsumiHOgraPL. The middle ear mucosal immune system in otitis media with effusion. Am J Otolaryngol1985; 6: 162–8.
14.
KilianPLOtternessIG. Cytokines and inflammation. In: LewisAJDohertyNSAckermanNR, eds. Therapeutic approaches to inflammatory disease. New York, NY: Elsevier, 1989: 14–7.
15.
ShawRJClarkRA. Interleukins and their interactions in inflammation. In: HeusenPMMurphyRC, eds. Handbook of inflammation. Vol 6. New York, NY: Elsevier, 1989: 245–67.
16.
OphirDHahnTSchattnerAWallachDAvielA. Tumor necrosis factor in middle ear effusions. Arch Otolaryngol Head Neck Surg1988; 114: 1256–8.
17.
YellonRFLeonardGMaruchaPT. Characterization of cytokines present in middle ear effusions. Laryngoscope1991; 101: 165–9.
18.
JuhnSKTolanCTGarvisWJCrossDSGiebinkGS. The levels of IL-1β in human middle ear effusions. Acta Otolaryngol [Suppl] (Stockh) 1992(suppl 493): 37–42.
19.
CatanzaroARyanABatcherSWassermanSI. The response to human rIL-1, rIL-2, and rTNF in the middle ear of guinea pigs. Laryngoscope1991; 101: 271–5.
20.
ParisMMFriedlandIREhrettS. Effect of interleukin-1 receptor antagonist and soluble tumor necrosis factor receptor in animal models of infection. J Infect Dis1995; 171: 161–9.
21.
BallSSPrazmaJDaisCGDRosbeKWPillsburyHC. Nitric oxide, a mediator of endotoxin-induced middle ear effusions. Laryngoscope1996; 106: 1021–7.
22.
EdamitsuSMatsukawaAOhkawaraSTakagiKNariuchiHYoshinagaM. Role of TNFα, IL-1, and IL-1ra in the mediation of leukocyte infiltration and increased vascular permeability in rabbits with LPS-induced pleurisy. Clin Immunol Immunopathol1995; 75: 68–74.
23.
HorganMJPalaceGPEverittJEMalikAB. TNF-α release in endotoxemia contributes to neutrophil-dependent pulmonary edema. Am J Physiol1993; 264: H1161–H1165.
24.
RampartMFiersWde SmetWHermanAG. Different pro-inflammatory profiles of interleukin 1 (IL-1) and tumor necrosis factor (TNF) in an in vivo model of inflammation. Agents Actions1989; 26: 186–8.
25.
UlichTRYiES. Endotoxin, interleukin-1, and tumor necrosis factor cause neutrophil-dependent microvascular leakage in postcapillary venules. Am J Pathol1992; 140: 659–63.
26.
UlichTRYinSRemickDGRussellDEisenbergSPKohnoT. Intratracheal administration of endotoxin and cytokines. IV. The soluble tumor necrosis factor receptor type I inhibits acute inflammation. Am J Pathol1993; 142: 1335–8.
27.
UlichTRYiESYinSSmithCRemickD. Intratracheal administration of endotoxin and cytokines. VII. The soluble interleukin-1 receptor and the soluble tumor necrosis factor receptor II (p80) inhibit acute inflammation. Clin Immunol Immunopathol1994; 72: 137–40.
