TNF can contribute to multiple features of ovalbumin-induced allergic inflammation of the airways in mice.
BACKGROUND
TNF is thought to contribute to airway hyperreactivity (AHR) and airway inflammation in asthma. However, studies with TNF-deficient or TNF receptor-deficient mice have not produced a clear picture of the role of TNF in the AHR associated with allergic inflammation in the mouse.


OBJECTIVE
We used a genetic approach to investigate the contributions of TNF to antigen-induced AHR and airway inflammation in mice on the C57BL/6 background.


METHODS
We analyzed features of airway allergic inflammation, including antigen-induced AHR, in C57BL/6 wild-type and TNF(-/-) mice, using 2 different methods for sensitizing the mice to ovalbumin (OVA).


RESULTS
In mice sensitized to OVA administered with the adjuvant aluminum hydroxide (alum), which develop IgE-independent and mast cell-independent allergic inflammation and AHR, we found no significant differences in OVA-induced AHR in C57BL/6-TNF(-/-) versus wild-type mice. By contrast, in mice sensitized to OVA without alum, which develop allergic inflammation that is significantly mast cell-dependent, C57BL/6-TNF(-/-) mice exhibited significant reductions versus wild-type mice in OVA-induced AHR to methacholine; numbers of lymphocytes, neutrophils, and eosinophils in bronchoalveolar lavage fluid; levels of myeloperoxidase, eosinophil peroxidase, and the cytokines IL-4, IL-5, and IL-17 in lung tissue; and histologic evidence of pulmonary inflammation.


CONCLUSIONS
In pulmonary allergic inflammation induced in mice immunized with OVA without alum, TNF significantly contributes to several features of the response, including antigen-induced inflammation and AHR.


CONCLUSIONS
Our findings in mice support the hypothesis that TNF can promote the allergic inflammation and AHR associated with asthma.
Nakae
Susumu
S
Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305-5324, USA.
Lunderius
Carolina
C
Ho
Lien H
LH
Schäfer
Beatrix
B
Tsai
Mindy
M
Galli
Stephen J
SJ
D000818:Animals; D001249:Asthma / Q000235:genetics* / Q000473:pathology; D016535:Bronchial Hyperreactivity / Q000235:genetics* / Q000473:pathology; D001991:Bronchitis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000032:analysis; D004195:Disease Models, Animal; D007073:Immunoglobulin E / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000473:pathology; D008407:Mast Cells / Q000276:immunology; D051379:Mice; D008817:Mice, Mutant Strains; D010047:Ovalbumin / Q000276:immunology; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics / Q000502:physiology; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000235:genetics / Q000502:physiology; D012130:Respiratory Hypersensitivity / Q000235:genetics* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000502:physiology*
D016207:Cytokines; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha; D007073:Immunoglobulin E; D010047:Ovalbumin