Role of tumor necrosis factor alpha in asthma

Babu, K. Suresh; Davies, Donna E.; Holgate, Stephen T.

doi:10.1016/j.iac.2004.06.010

Cited by 60 publications

(27 citation statements)

References 81 publications

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“…In the model shown in figure 1, Th2 cytokines play a key role in amplifying the tissue-specific features of asthma, such as goblet cell hyperplasia and transformation of fibroblasts to myofibroblasts. Placing airway tissue-specific events at the centre of asthma pathogenesis provides an explanation for the incomplete effectiveness of inhaled corticosteroids and the therapeutic synergy observed between inhaled corticosteroids and long-acting b 2 -adrenoceptor agonists, the relatively poor correlation of submucosal eosinophil numbers with disease activity or chronicity, the presence of ''remodelling'' changes in the airways at the inception of asthma in the relative absence of eosinophils, the occurrence of asthma in the absence of atopy (as is prominent in occupational and aspirin-intolerant asthma) and the recently discovered efficacy of anti-TNF-a observed in patients with severe corticosteroid-dependent disease [24]. A key role of epithelial-mesenchymal communication in asthma is further endorsed by the observation that six of the seven asthma susceptibility genes discovered by positional cloning are localised to the EMTU, stating this in the form of the following hypothesis.…”

Section: Epithelial Mesenchymal Communicationmentioning

confidence: 99%

Local genetic and environmental factors in asthma disease pathogenesis: chronicity and persistence mechanisms

Holgate¹,

Davies²,

Powell³

et al. 2007

European Respiratory Journal

119

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While asthma is an inflammatory disorder of the airways usually associated with atopy, an important additional component is involvement of the epithelium and underlying mesenchyme acting as a trophic unit (EMTU).In addition to allergens, a wide range of environmental factors interact with the EMTU, such as virus infections, environmental tobacco smoke and pollutants, to initiate tissue damage and aberrant repair responses that are translated into remodelling of the airways. While candidate gene association studies have revealed polymorphic variants that influence asthmatic inflammation, positional cloning of previously unknown genes is identifying a high proportion of novel genes in the EMTU.Dipeptidyl peptidase (DPP) 10 and disintegrin and metalloproteinase (ADAM)33 are newly identified genes strongly associated with asthma that are preferentially expressed in the airway epithelium and underlying mesenchyme, respectively.Also of increasing importance is the recognition that genes associated with asthma and atopy have important interactions with the environment through epigenetic mechanisms that influence their expression. This type of research will not only identify biomarkers of different types of asthma across the full range of phenotypic expression, but will also identify novel therapeutic targets that could influence the natural history of the heterogenes lung disease.

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Section: Epithelial Mesenchymal Communicationmentioning

confidence: 99%

Local genetic and environmental factors in asthma disease pathogenesis: chronicity and persistence mechanisms

Holgate¹,

Davies²,

Powell³

et al. 2007

European Respiratory Journal

119

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“…The proinflammatory activities of TNF-α including leukocyte recruitment through the upregulation of adhesion molecules on endothelial cells and induction of cytokine and chemokine synthesis seem involved in the pathogenesis of asthma [76]. Elevated levels of TNF-α have been detected in bronchoalveolar lavage fluid and biopsy samples in asthmatic patients [77].…”

Section: Proinflammatory Cytokines In the Allergic Inflammationmentioning

confidence: 99%

Role of Cytokines in Allergic Airway Inflammation

Nakajima

Takatsu

2006

Int Arch Allergy Immunol

138

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Asthma is characterized by intense infiltration of eosinophils and CD4+ T cells into the submucosal tissue of airways. Accumulating evidence indicates that T helper type 2 cell-derived cytokines such as interleukin (IL)-4, IL-5 and IL-13 play critical roles in orchestrating and amplifying allergic inflammation in asthma. In addition, it has been suggested that newly identified cytokines including thymic stromal lymphopoietin, IL-25 and IL-33 are involved in the induction of allergic inflammation in asthma. In this review, we discuss the role of individual cytokines in the pathogenesis of asthma.

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“…1,2 In human beings, TNF can induce lung neutrophil infiltration and increase airway hyperreactivity (AHR) to methacholine in normal individuals 3 ; some patients with asthma exhibit elevated serum TNF 4 ; TNF immunoreactive cells (mostly mast cells) were ;6-fold increased in airway submucosa biopsies of patients with asthma versus normal controls 5 ; and anti-TNF therapy reduced asthma severity in some subjects. [6][7][8][9][10] However, experiments in TNF-deficient or TNF receptor (TNFR)-deficient mice have not fully clarified the role of TNF in pulmonary allergic inflammation, or the associated AHR, in mice. In BALB/c mice sensitized with ovalbumin (OVA) without aluminum hydroxide (alum), treatment with anti-TNF neutralizing antibodies did not significantly reduce either AHR or numbers of bronchoalveolar lavage fluid (BALF) eosinophils after OVA challenge.…”

mentioning

confidence: 99%