TNF-α contributes to the development of allergic rhinitis in mice

Abstract

Background: Allergic rhinitis is an inflammation involving TH2-type cytokine production, with pathologic eosinophil infiltration in the nasal mucosa. Although TNF-α is thought to be a pro-inflammatory cytokine, the relationship between TNF-α and allergic rhinitis has not been clarified. Objectives: The role of TNF-α in a murine model of ovalbumin (OVA)-sensitized allergic rhinitis was investigated by using mice deficient in the gene encoding TNF-α (TNF-α–/– mice). Methods: Both wild-type (TNF-α+/+) and TNF-α–/– mice were sensitized with OVA by means of intraperitoneal injection. They were then challenged with intranasal OVA, and various allergic responses were assessed. Results: The production of OVA-specific IgE in the serum (P < .05) and the frequency of sneezes (P < .05) and nasal rubs (P < .05) decreased significantly in TNF-α–/– mice after OVA sensitization compared with that in TNF-α+/+ mice (P < .05). The mRNA expression of IL-4, IL-10, and eotaxin in nasal mucosa in TNF-α–/– mice was also significantly suppressed compared with that in TNF-α+/+ mice after OVA sensitization (P < .05). Furthermore, the expression of both endothelial-leukocyte adhesion molecule 1 and vascular cell adhesion molecule 1 mRNA in the nasal mucosa was significantly suppressed (P < .05), although intercellular adhesion molecule 1 mRNA expression did not decrease significantly in TNF-α–/– mice compared with that in TNF-α+/+ mice after OVA sensitization. In addition, the effect of TNF-α on endothelial-leukocyte adhesion molecule 1 and vascular cell adhesion molecule 1 expression by means of Western blot analysis was compatible with the mRNA results. Pathologically, eosinophil infiltration in nasal mucosa was significantly restricted in TNF-α–/– mice compared with in TNF-α+/+ mice after OVA sensitization (P < .05). Conclusion: TNF-α is necessary for antigen-specific IgE production and for the induction of TH2-type cytokines and chemokines. Furthermore, TNF-α might be important for the expression of adhesion molecules to recruit eosinophils to the allergic inflammatory site. We conclude that the lack of TNF-α inhibited the development of allergic rhinitis. (J Allergy Clin Immunol 2003;112:134-40.)