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Immunol Cell Biol. 2001 Apr;79(2):132-40.

Tumour necrosis factor-alpha: the role of this multifunctional cytokine in asthma.

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Faculty of Medicine, University of New South Wales and Department of Respiratory Medicine, Prince of Wales Hospital, Randwick, New South Wales, Australia.


Tumour necrosis factor-alpha (TNF-alpha) is recognized as an important mediator in many cytokine- dependent inflammatory events. It is known that TNF-alpha is released in allergic responses from both mast cells and macrophages via IgE-dependent mechanisms, and elevated levels have been demonstrated in the bronchoalveolar fluid (BALF) of asthmatic subjects undergoing allergen challenge. Inhaled TNF-alpha increases airway responsiveness to methacholine in normal and asthmatic subjects associated with a sputum neutrophilia. Additional data indicate that TNF-alpha can upregulate adhesion molecules, facilitate the immigration of inflammatory cells into the airway wall and activate pro-fibrotic mechanisms in the subepithelium. These data suggest that TNF-alpha plays a role in the initiation of allergic asthmatic airway inflammation and the generation of airway hyper-reactivity. In addition, polymorphisms of the TNF-alpha gene 5' untranslated region, particularly at -308 bp, have been described as being associated with asthma. This polymorphism is associated with increased levels of TNF-alpha, but as yet, no asthma studies have demonstrated a phenotypic difference between those individuals with the polymorphism and those with the wild type gene. The TNF receptors (TNF-R p55 and p75), also known as CD120a and b, have also been shown to be present in the lung, but their functional importance is only just emerging. In asthma, TNF may function as a pro-inflammatory cytokine that causes the recruitment of neutrophils and eosinophils. Treatment directed specifically at a reduction in TNF-alpha activity may conceivably be useful as a glucocorticosteroid-sparing asthma therapy.

[Indexed for MEDLINE]

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