TITLE

Tumour necrosis factor (TNFα) as a novel therapeutic target in symptomatic corticosteroid dependent asthma

AUTHOR(S)
Howarth, P. H.; Babu, K. S.; Arshad, H. S.; Lou, L.; Buckley, M.; McConnell, W.; Beckett, P.; Ali, M. Al.; Chauhan, A.; Wilson, S. J.; Reynolds, A.; Davies, D. E.; Holgate, S. T.
PUB. DATE
December 2005
SOURCE
Thorax;Dec2005, Vol. 60 Issue 12, p1012
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Background: Tumour necrosis factor α (TNFα) is a major therapeutic target in a range of chronic inflammatory disorders characterised by a Th1 type immune response in which TNFα is generated in excess. By contrast, asthma is regarded as a Th2 type disorder, especially when associated with atopy. However, as asthma becomes more severe and chronic, it adopts additional characteristics including corticosteroid refractoriness and involvement of neutrophils suggestive of an altered inflammatory profile towards a Th1 type response, incriminating cytokines such as TNFα. Methods: TNFα levels in bronchoalveolar lavage (BAL) fluid of 26 healthy controls, 42 subjects with mild asthma and 20 with severe asthma were measured by immunoassay, and TNFα gene expression was determined in endobronchial biopsy specimens from 14 patients with mild asthma and 14 with severe asthma. The cellular localisation of TNFα was assessed by immunohistochemistry. An open label uncontrolled clinical study was then undertaken in 17 subjects with severe asthma to evaluate the effect of 12 weeks of treatment with the soluble TNFα receptor-IgG1Fc fusion protein, etanercept. Results: TNFα levels in BAL fluid, TNFα gene expression and TNFα immunoreative cells were increased in subjects with severe corticosteroid dependent asthma. Etanercept treatment was associated with improvement in asthma symptoms, lung function, and bronchial hyperresponsiveness. Conclusions: These findings may be of clinical significance in identifying TNFα as a new therapeutic target in subjects with severe asthma. The effects of anti-TNF treatment now require confirmation in placebo controlled studies.
ACCESSION #
19120641

 

Related Articles

  • Macrophages are important mediators of either tumor- or inflammation-induced lymphangiogenesis. Ji, Rui-Cheng // Cellular & Molecular Life Sciences;Mar2012, Vol. 69 Issue 6, p897 

    The lymphatic system provides important functions for tissue fluid homeostasis and immune response. Lymphangiogenesis, the formation of new lymphatics, comprises a series of complex cellular events in vitro or in vivo, e.g., proliferation, differentiation, and sprouting. Recent evidence has...

  • Novel treatment for severe asthma. Bowden, Rachel // GP: General Practitioner;10/7/2005, p18 

    The article cites a British study which states that patients with severe asthma could benefit from treatment with tumor necrosis factor (TNF) blockers. The study found higher levels of the inflammatory cytokine TNF-alpha in patients with severe asthma than in patients with mild asthma. This...

  • Subclinical keratoconus and inflammatory molecules from tears. I Lema // British Journal of Ophthalmology;Jun2009, Vol. 93 Issue 6, p820 

    BACKGROUND/AIMS: Tissue degradation in corneal thinning disorders, such as keratoconus (KC), involves the expression of inflammatory mediators. The purpose of this study was to determine the levels of proinflammatory cytokines and matrix metalloproteinase 9 (MMP-9) in tears from both eyes of...

  • Low-level laser therapy (LLLT) acts as cAMP-elevating agent in acute respiratory distress syndrome. Lima, Flávia; Moreira, Leonardo; Villaverde, A.; Albertini, Regiane; Castro-Faria-Neto, Hugo; Aimbire, Flávio // Lasers in Medical Science;May2011, Vol. 26 Issue 3, p389 

    The aim of this work was to investigate if the low-level laser therapy (LLLT) on acute lung inflammation (ALI) induced by lipopolysaccharide (LPS) is linked to tumor necrosis factor (TNF) in alveolar macrophages (AM) from bronchoalveolar lavage fluid (BALF) of mice. LLLT has been reported to...

  • Novel pathway compendium analysis elucidates mechanism of pro-angiogenic synthetic small molecule. Kristen A. Wieghaus; Erwin P. Gianchandani; Mikell A. Paige; Milton L. Brown; Edward A. Botchwey; Jason A. Papin // Bioinformatics;Oct2008, Vol. 24 Issue 20, p2384 

    Motivation: Computational techniques have been applied to experimental datasets to identify drug mode-of-action. A shortcoming of existing approaches is the requirement of large reference databases of compound expression profiles. Here, we developed a new pathway-based compendium analysis that...

  • Elevated Levels of Type II Soluble Tumor Necrosis Factor Receptors in the Bronchoalveolar Lavage Fluids of Patients with Sarcoidosis. Hino, T.; Nakamura, H.; Shibata, Y.; Abe, S.; Kato, S.; Tomoike, H. // Lung;1997, Vol. 175 Issue 3, p187 

    Since tumor necrosis factor (TNF) is known to be involved in granuloma formation in sarcoidosis, and soluble TNF receptors (sTNF-Rs) inhibit TNF action in vivo, we evaluated the levels of sTNF-Rs in the bronchoalveolar lavage fluids (BALF) of 31 subjects using an enzyme-linked immunosorbent...

  • Tumor Necrosis Factor-α-Converting Enzyme: Its Role in Community-Acquired Pneumonia. Greene, Catherine; Lowe, Gregory; Taggart, Clifford; Gallagher, Paula; McElvaney, Noel; O'Neill, Shane // Journal of Infectious Diseases;12/15/2002, Vol. 186 Issue 12, p1790 

    Bronchoalveolar lavage fluid recovered from infected and uninvolved lungs of patients with community-acquired pneumonia (CAP; n = 16) on day 6 ± 0.8 was analyzed for cytokine, soluble receptor, and antagonist levels. The role of tumor necrosis factor (TNF)-α-converting enzyme (TACE) in the...

  • Retnla Overexpression Attenuates Allergic Inflammation of the Airway. Lee, Mi-Ran; Shim, Dahee; Yoon, Jihye; Jang, Hyung Seok; Oh, Se-Woong; Suh, Suk Hyo; Choi, Jae-Hoon; Oh, Goo Taeg // PLoS ONE;Nov2014, Vol. 9 Issue 11, p1 

    Resistin-like molecule alpha (Retnla), also known as ‘Found in inflammatory zone 1’, is a secreted protein that has been found in bronchoalveolar lavage (BAL) fluid of ovalbumin (OVA)-induced asthmatic mice and plays a role as a regulator of T helper (Th)2-driven inflammation....

  • The role of a soluble TNFalpha receptor fusion protein (etanercept) in corticosteroid refractory asthma: a double blind, randomised, placebo controlled trial. Morjaria, J. B.; Chauhan, A. J.; Babu, K. S.; Polosa, A.; Davies, D. E.; Holgate, S. T.; Polosa, R // Thorax;Jul2008, Vol. 63 Issue 7, p584 

    Aim: Tumour necrosis factor alpha (TNFalpha) is a cytokine recognised as a therapeutic target in chronic inflammatory diseases.Methods: A randomised, double blind, placebo controlled parallel group trial is reported of etanercept (an IgG1-TNF p75 receptor fusion...

Share

Read the Article

Courtesy of VIRGINIA BEACH PUBLIC LIBRARY AND SYSTEM

Sign out of this library

Other Topics