Effects of tumor necrosis factor alpha antagonist, platelet activating factor antagonist, and nitric oxide synthase inhibitor on experimental otitis media with effusion.

Abstract

OBJECTIVES:

We studied the inflammatory responses in otitis media with effusion induced by lipopolysaccharide (LPS) in rats, and compared the preventive effects of tumor necrosis factor (TNF) soluble receptor type I (sTNFRI, a TNF-alpha antagonist), platelet activating factor antagonist, and the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME).

METHODS:

We used 2 control groups of Sprague Dawley rats (untreated and saline-treated) and 4 experimental groups, which all received an intratympanic injection of LPS, followed in 3 groups by experimental treatment of the same ear. The LPS group had no additional treatment. The L-NAME group received intraperitoneal injection of L-NAME and was reinjected after 12 hours. The A-85783 group was first given an intraperitoneal injection of A-85783. The sTNFRI group was first given an intratympanic injection of sTNFRI. Twenty-four hours after the initial intratympanic injection of LPS, temporal bones from each group were examined histopathologically and the vascular permeability of the middle ear mucosa was measured by Evans blue vital dye staining.

RESULTS:

The L-NAME, A-85783, and sTNFRI groups showed significantly reduced capillary permeability, subepithelial edema, and infiltration of inflammatory cells in comparison with the LPS group. There were no differences in capillary permeability, subepithelial edema, or infiltration of inflammatory cells between the A-85783 and sTNFRI groups. The L-NAME group showed no difference in vascular permeability or subepithelial edema in comparison with the A-85783 and sTNFRI groups, but showed more infiltration of inflammatory cells.

CONCLUSIONS:

We conclude that sTNFRI, A-85783, and L-NAME can be proposed as alternative future treatments for otitis media with effusion. However, L-NAME may be the least effective of these agents.

• Authors: Dong-Hyun Kim, Yong-Soo Park, Eun-Ju Jeon, Sang-Won Yeo, Ki-Hong Chang, Seung Kyun Lee
• Journal: The Annals of otology, rhinology, and laryngology (Ann Otol Rhinol Laryngol) Vol. 115 Issue 8 Pg. 617-23 (Aug 2006) ISSN: 0003-4894 [Print] United States
• PMID: 16944661 (Publication Type: Journal Article)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Enzyme Inhibitors
• Immunoglobulin G
• Indoles
• Lipopolysaccharides
• Platelet Activating Factor
• Receptors, Tumor Necrosis Factor
• Thiazoles
• Tumor Necrosis Factor-alpha
• Nitric Oxide Synthase
• A 85783.0
• Etanercept
• NG-Nitroarginine Methyl Ester

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (pharmacology)
• Capillary Permeability (drug effects)
• Ear, Middle (blood supply, drug effects)
• Enzyme Inhibitors (pharmacology)
• Etanercept
• Immunoglobulin G (pharmacology)
• Immunohistochemistry
• Indoles (pharmacology)
• Injections, Intralesional
• Injections, Intraperitoneal
• Lipopolysaccharides (toxicity)
• Multivariate Analysis
• NG-Nitroarginine Methyl Ester (pharmacology)
• Nitric Oxide Synthase (antagonists & inhibitors, pharmacology)
• Otitis Media with Effusion (chemically induced, pathology, prevention & control)
• Photomicrography
• Platelet Activating Factor (antagonists & inhibitors, pharmacology)
• Pseudomonas aeruginosa
• Rats
• Rats, Sprague-Dawley
• Receptors, Tumor Necrosis Factor
• Thiazoles (pharmacology)
• Tumor Necrosis Factor-alpha (antagonists & inhibitors, pharmacology)
• Tympanic Membrane (drug effects)