Tumour necrosis factor-α blockade suppresses murine allergic airways inflammation

S. Hutchison, B.S.W. Choo-Kang, R.V. Bundick, A.J. Leishman, J.M. Brewer, I.B. McInnes, P. Garside

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Abstract

Asthma is a heterogeneous disease that has been increasing in incidence throughout western societies and cytokines, including proinflammatory tumour necrosis factor alpha (TNF-a), have been implicated in the pathogenesis of asthma. Anti-TNF-a therapies have been established successfully in the clinic for diseases such as rheumatoid arthritis and Crohn's disease. TNF-ablocking strategies are now being trialled in asthma; however, their mode of action is poorly understood. Based on the observation that TNF-a induces lymph node hypertrophy we have attempted to investigate this as a mechanism of action of TNF-a in airway inflammation by employing twomodels of murine airway inflammation, that we have termed short and long models, representing severe and mild/moderate asthma, respectively. The models differ by their immunization schedules. In the short model, characterized by eosinophilic and neutrophilic airway inflammation the effect of TNF-a blockade was a reduction in draining lymph node (DLN) hypertrophy, eosinophilia, interleukin (IL)-5 production and immunoglobulin E (IgE) production. In the long model, characterized by eosinophilic inflammation, TNF-a blockade produced a reduction in DLN hypertrophy and IL-5 production but had limited effects on eosinophilia and IgE production. These results indicate that anti-TNF-a can suppress DLN hypertrophy and decrease airway inflammation. Further investigations showed that anti-TNF-a-induced inhibition of DLN hypertrophy cannot be explained by preventing l-selectindependent capture of lymphocytes into the DLN. Given that overall TNF blockade was able to suppress the short model (severe) more effectively than the long model (mild/moderate), the results suggest that TNF-a blocking therapies may be more effective in the treatment of severe asthma.
Original languageEnglish
Pages (from-to)114-122
Number of pages8
JournalClinical and Experimental Immunology
Volume151
Issue number1
DOIs
Publication statusPublished - Jan 2008

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Keywords

  • airway hypersensitivity
  • airway inflammation
  • IgE
  • T cells
  • TNF-a
  • tumour necrosis
  • inflamation
  • asthma

Cite this

Hutchison, S., Choo-Kang, B. S. W., Bundick, R. V., Leishman, A. J., Brewer, J. M., McInnes, I. B., & Garside, P. (2008). Tumour necrosis factor-α blockade suppresses murine allergic airways inflammation. Clinical and Experimental Immunology, 151(1), 114-122. https://doi.org/10.1111/j.1365-2249.2007.03509.x