TNF-alpha contributes to the development of allergic rhinitis in mice.
BACKGROUND
Allergic rhinitis is an inflammation involving T(H)2-type cytokine production, with pathologic eosinophil infiltration in the nasal mucosa. Although TNF-alpha is thought to be a pro-inflammatory cytokine, the relationship between TNF-alpha and allergic rhinitis has not been clarified.


OBJECTIVE
The role of TNF-alpha in a murine model of ovalbumin (OVA)-sensitized allergic rhinitis was investigated by using mice deficient in the gene encoding TNF-alpha (TNF-alpha(-/-) mice).


METHODS
Both wild-type (TNF-alpha(+/+)) and TNF-alpha(-/-) 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-alpha(-/-) mice after OVA sensitization compared with that in TNF-alpha(+/+) mice (P <.05). The mRNA expression of IL-4, IL-10, and eotaxin in nasal mucosa in TNF-alpha(-/-) mice was also significantly suppressed compared with that in TNF-alpha(+/+) 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-alpha(-/-) mice compared with that in TNF-alpha(+/+) mice after OVA sensitization. In addition, the effect of TNF-alpha 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-alpha(-/-) mice compared with in TNF-alpha(+/+) mice after OVA sensitization (P <.05).


CONCLUSIONS
TNF-alpha is necessary for antigen-specific IgE production and for the induction of T(H)2-type cytokines and chemokines. Furthermore, TNF-alpha might be important for the expression of adhesion molecules to recruit eosinophils to the allergic inflammatory site. We conclude that the lack of TNF-alpha inhibited the development of allergic rhinitis.
Iwasaki
Masao
M
Department of Otorhinolaryngology, Gifu University School of Medicine, Gifu.
Saito
Kuniaki
K
Takemura
Masao
M
Sekikawa
Kenji
K
Fujii
Hidehiko
H
Yamada
Yasuhiro
Y
Wada
Hisayasu
H
Mizuta
Keisuke
K
Seishima
Mitsuru
M
Ito
Yatsuji
Y
D000818:Animals; D015815:Cell Adhesion Molecules / Q000235:genetics; D018925:Chemokines / Q000235:genetics; D016207:Cytokines / Q000235:genetics; D004802:Eosinophilia / Q000209:etiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D012221:Rhinitis, Allergic, Perennial / Q000209:etiology* / Q000276:immunology; D006255:Rhinitis, Allergic, Seasonal / Q000209:etiology* / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D015815:Cell Adhesion Molecules; D018925:Chemokines; D016207:Cytokines; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D010047:Ovalbumin