Effects of a TNF-α Antagonist on Rhinosinusitis Model

Abstract

Objective: Tumor necrosis factor (TNF) is an important mediator of inflammation and is produced by macrophages in response to stimuli such as bacterial lipopolysaccharide (LPS) and viruses. This study examined the effects of a TNF-α antagonist on the LPS-induced inflammatory response in the nasal cavity and sinus of rats.

Method: Experimental groups received an instillation of lipopolysaccharide (LPS) plus an intramuscular injection of amoxicillin/clavulanate (antibiotic group), an instillation of sTNFRI (sTNFRI group), an instillation of sTNFRI and an injection of amoxicillin/clavulanate (sTNFRI/antibiotic group), or no additional treatment (LPS group). Histopathological changes were determined using hematoxylin-eosin and periodic acid-Schiff (PAS) staining. Leakage of exudate was determined using fluorescence microscopy. Vascular permeability was measured using the Evans blue dye technique. Expression of MUC5AC was measured using reverse transcriptase PCR.

Results: The sTNFRI, antibiotic, and sTNFRI/antibiotic groups had significantly less capillary permeability, mucosal edema, PAS staining, and expression of MUC5AC than the LPS group. There were no differences in capillary permeability, mucosal edema, PAS staining, and MUC5AC expression between the sTNFRI and sTNFRI/antibiotic groups. The antibiotic group had PAS staining similar to that of the sTNFRI and sTNFRI/antibiotic groups but had a greater increase in capillary permeability, mucosal edema, and MUC5AC expression.

Conclusion: Intranasal administration of sTNFRI reduces inflammatory activity, including elevated microvascular permeability and tissue edema, and mucus hypersecretion, including production of mucosubstance and expression of MUC5AC, in LPS-induced rhinosinusitis in rats. Results demonstrate that intranasal administration of sTNFRI reduces inflammatory activity and mucus hypersecretion in LPS-induced rhinosinusitis in rats.