Evidence of a Role of Tumor Necrosis Factor α in Refractory Asthma

Berry, Michael A.; Hargadon, Beverley; Shelley, Maria; Parker, Debbie; Shaw, Dominick; Green, Ruth H.; Bradding, Peter; Brightling, Christopher E.; Wardlaw, Andrew J.; Pavord, Ian D.

doi:10.1056/nejmoa050580

Cited by 757 publications

(553 citation statements)

References 27 publications

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“…We are, however, unable to examine the effect of in utero cigarette smoke exposure, which is a risk factor for both depression and asthma in the offspring (43,44). Depression is also associated with high systemic levels of inflammatory cytokines, particularly TNFa, which, in turn, has a pathogenic role in asthma (45,46). Finally, a potential neuroendocrine mechanism involves depression-related alteration in the hypothalamic-pituitary-adrenal axis that For definition of abbreviation, see Table 2.…”

Section: Discussionmentioning

confidence: 99%

Depression and Risk of Incident Asthma in Adults. The CARDIA Study

Brunner

Schreiner

Sood

et al. 2014

Am J Respir Crit Care Med

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Rationale: Asthma is associated with depression, but the temporality of the association has not been established.Objectives: To examine the association between prevalent elevated depressive symptoms and incident asthma, and between prevalent asthma and incident elevated depressive symptoms in a cohort of young and middle-aged adults.Methods: We examined the longitudinal association between asthma and depressive symptoms bidirectionally in the Coronary Artery Risk Development in Young Adults (CARDIA) cohort. First, 3,614 participants, free of asthma, were classified by elevated depressive symptoms at the CARDIA Year-5 exam (n = 856 elevated vs. 2,758 not elevated; ages 23-35 yr) and followed for 20 years to incident asthma. Then, 3,016 participants, free of elevated depressive symptoms, were classified by self-reported current asthma status (n = 188 prevalent vs. 2,828 not prevalent) at the CARDIA Year-5 exam and followed for 20 years until onset of elevated depressive symptoms. Measurements and Main Results:The relative hazard of incident asthma among those with elevated depressive symptoms was 1.26 (95% confidence interval [CI] = 1.02-1.56) after adjustment for covariates. When depressive status was modeled as the total number of reports of elevated depressive symptoms before the onset of asthma, the adjusted hazard ratio was 1.15 (95% CI = 1.02-1.29). The hazard of incident elevated depressive symptoms for those with asthma was no different than the hazard in those without asthma (adjusted hazard ratio = 0.92; 95% CI = 0.70-1.20).Conclusions: This longitudinal observational study points to depression as a marker of risk for incident adult-onset asthma. On the other hand, prevalent asthma is not associated with incident adultonset depression.

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Section: Discussionmentioning

confidence: 99%

Depression and Risk of Incident Asthma in Adults. The CARDIA Study

Brunner

Schreiner

Sood

et al. 2014

Am J Respir Crit Care Med

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“…This action of TNF␣ may contribute in part to the airway hyperresponsiveness induced by this cytokine. intracellular calcium; pulmonary afferent; transient receptor potential vanilloid type 1; airway inflammation; asthma AN IMPORTANT ROLE OF TNF␣ in the pathogenesis of allergic asthma has been extensively documented (6,9,28,47). TNF␣ can be released from a variety of cell types in the airways, particularly macrophages, monocytes, and mast cells.…”

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confidence: 99%

“…AN IMPORTANT ROLE OF TNF␣ in the pathogenesis of allergic asthma has been extensively documented (6,9,28,47). TNF␣ can be released from a variety of cell types in the airways, particularly macrophages, monocytes, and mast cells.…”

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confidence: 99%

Calcium transient evoked by TRPV1 activators is enhanced by tumor necrosis factor-α in rat pulmonary sensory neurons

Gu²,

Lin³

et al. 2010

American Journal of Physiology-Lung Cellular and Molecular Phys

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Hu Y, Gu Q, Lin RL, Kryscio R, Lee LY. Calcium transient evoked by TRPV1 activators is enhanced by tumor necrosis factor-␣ in rat pulmonary sensory neurons. Am J Physiol Lung Cell Mol Physiol 299: L483-L492, 2010. First published July 16, 2010 doi:10.1152/ajplung.00111.2010.-TNF␣, a proinflammatory cytokine known to be involved in the pathogenesis of allergic asthma, has been shown to induce hyperalgesia in somatic tissue via a sensitizing effect on dorsal root ganglion neurons expressing transient receptor potential vanilloid type 1 receptor (TRPV1). Because TRPV1-expressing pulmonary sensory neurons play an important role in regulating airway function, this study was carried out to determine whether TNF␣ alters the sensitivity of these neurons to chemical activators. Responses of isolated nodose and jugular ganglion neurons innervating the rat lungs were determined by measuring the transient increase in intracellular Ca 2ϩ concentration ([Ca 2ϩ ]i). Our results showed the following. 1) A pretreatment with TNF␣ (50 ng/ml) for ϳ24 h increased significantly the peak ⌬[Ca 2ϩ ]i evoked by capsaicin (Cap) in these neurons. A pretreatment with the same concentration of TNF␣ for a longer duration (ϳ48 h) did not further increase the response, but pretreatment for a shorter duration (1 h) or with a lower concentration (25 ng/ml, 24 h) failed to enhance the Cap sensitivity.2) The same TNF␣ pretreatment also induced similar but less pronounced and less uniform increases in the responses to acid (pH 6.5-5.5), 2-aminoethoxydiphenyl borate (2-APB), a common activator of TRPV1, V2, and V3 channels, and allyl isothiocyanate (AITC), a selective activator of TRPA1 channel. 3) In sharp contrast, the responses to ATP, ACh, and KCl were not affected by TNF␣. 4) The TNF␣-induced hypersensitivity to Cap was not prevented by pretreatment with indomethacin (30 M). 5) The immunoreactivity to both TNF receptor types 1 and 2 were detected in rat vagal pulmonary sensory neurons. In conclusion, prolonged treatment with TNF␣ induces a pronounced potentiating effect on the responses of isolated pulmonary sensory neurons to TRPV1 activators. This action of TNF␣ may contribute in part to the airway hyperresponsiveness induced by this cytokine. intracellular calcium; pulmonary afferent; transient receptor potential vanilloid type 1; airway inflammation; asthma AN IMPORTANT ROLE OF TNF␣ in the pathogenesis of allergic asthma has been extensively documented (6,9,28,47). TNF␣ can be released from a variety of cell types in the airways, particularly macrophages, monocytes, and mast cells. TNF␣, either newly synthesized or preformed and stored constitutively within the mast cell granules, is coreleased with other potent mediators such as histamine and tryptase via the IgE-dependent mechanism (9, 21, 47). TNF␣ was detected in bronchoalveolar lavage fluid, sputum, exhaled breath condensate, and serum of asthmatic patients during asthmatic attack or following antigen inhalation challenge (12,33,39). Furthermore, it has been shown that TNF␣ is releas...

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“…Regarding the role of TNF-a in human asthma, TNF-a has been reported to induce epithelial apoptosis and shedding [27]. Additionally, recent studies have demonstrated that anti-TNF-a therapy in patients with asthma markedly improved asthma symptoms, lung function, and AHR, in which the most striking feature of anti-TNF therapy was the improvement in AHR [28,29], further indicating an important role of TNF-a in the development of AHR.…”

Section: Discussionmentioning

confidence: 99%

Mast cells play a key role in the developmentof late airway hyperresponsiveness through TNF‐αin a murine model of asthma

Kim

Kang

et al. 2007

Eur J Immunol

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We have investigated the role of TNF‐α in mast cell‐mediated late airway hyperresponsiveness (AHR) using mast cell‐deficient WBB6F1‐W/Wv (W/Wv) mice in a murine model of asthma, which exhibits a biphasic increase in AHR. TNF‐α levels in the airway and magnitude of late AHR in response to airway allergen challenge were severely impaired in W/Wv mice compared to their littermates. In addition to TNF‐α, cytosolic phospholipase A2 (cPLA2) phosphorylation and enzymatic activity in the lungs were also impaired in W/Wv mice. Either anti‐TNF‐α antibody or an inhibitor of cPLA2 abolished late AHR in congeneic +/+ mice. Intratracheal administration of TNF‐α resulted in increases in late AHR, cPLA2 phosphorylation, cPLA2 activity, and phosphorylation of mitogen‐activated protein kinases. Mast cell replacement restored airway TNF‐α level, cPLA2 phosphorylation and enzymatic activity in the lungs as well as late AHR in W/Wv mice. These data indicate that mast cells play a key role in the development of late AHR through liberation of TNF‐α.

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Evidence of a Role of Tumor Necrosis Factor α in Refractory Asthma

Abstract: Patients with refractory asthma have evidence of up-regulation of the TNF-alpha axis. (ClinicalTrials.gov number, NCT00276029.).

Cited by 757 publications

References 27 publications

Depression and Risk of Incident Asthma in Adults. The CARDIA Study

Depression and Risk of Incident Asthma in Adults. The CARDIA Study

Calcium transient evoked by TRPV1 activators is enhanced by tumor necrosis factor-α in rat pulmonary sensory neurons

Mast cells play a key role in the developmentof late airway hyperresponsiveness through TNF‐αin a murine model of asthma

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