Tumour necrosis factor-alpha blockade suppresses murine allergic airways inflammation

Hutchison, S., Choo-Kang, B.S.W., Bundick, R.V., Leishman, A.J., Brewer, J.M., McInnes, I. and Garside, P. (2008) Tumour necrosis factor-alpha blockade suppresses murine allergic airways inflammation. Clinical and Experimental Immunology, 151(1), pp. 114-122. (doi: 10.1111/j.1365-2249.2007.03509.x) (PMID:17931392)

Abstract

Asthma is a heterogeneous disease that has been increasing in incidence throughout western societies and cytokines, including proinflammatory tumour necrosis factor alpha (TNF-alpha), have been implicated in the pathogenesis of asthma. Anti-TNF-alpha therapies have been established successfully in the clinic for diseases such as rheumatoid arthritis and Crohn's disease. TNF-alpha-blocking strategies are now being trialled in asthma; however, their mode of action is poorly understood. Based on the observation that TNF-alpha induces lymph node hypertrophy we have attempted to investigate this as a mechanism of action of TNF-alpha in airway inflammation by employing two models 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-alpha 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-alpha 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-alpha can suppress DLN hypertrophy and decrease airway inflammation. Further investigations showed that anti-TNF-alpha-induced inhibition of DLN hypertrophy cannot be explained by preventing l-selectin-dependent 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-alpha blocking therapies may be more effective in the treatment of severe asthma.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: McInnes, Professor Iain and Garside, Professor Paul and Brewer, Professor James
• Authors: Hutchison, S., Choo-Kang, B.S.W., Bundick, R.V., Leishman, A.J., Brewer, J.M., McInnes, I., and Garside, P.
• College/School: College of Medical Veterinary and Life Sciences; College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Clinical and Experimental Immunology
• Publisher: Wiley-Blackwell Publishing Ltd.
• ISSN: 0009-9104