TNF-alpha as a promising therapeutic target in chronic asthma: a lesson from rheumatoid arthritis

TNF-alpha (tumour necrosis factor-alpha) is known to play a critical role in the pathogenic mechanisms of a number of chronic inflammatory diseases, including RA (rheumatoid arthritis), Crohn's disease and psoriasis. The notion that TNF-alpha is released in allergic responses from both mast cells and macrophages via IgE-dependent mechanisms, the demonstration that elevated levels of TNF-alpha are frequently observed in bronchoalveolar fluid of asthmatic subjects undergoing allergen challenge and the results from exposure studies of TNF-alpha in vivo showing increases in airway responsiveness in both normal and asthmatic subjects emphasize the importance of TNF-alpha in the initiation of allergic asthmatic airway inflammation and the generation of airway hyper-responsiveness. Drugs targeting TNF-alpha have been developed to neutralize the deleterious effects of this inflammatory cytokine and have proved to be safe and effective in the treatment of patients with RA, Crohn's disease and psoriasis refractory to conventional treatments. Biological therapies blocking TNF-alpha are likely to constitute a considerable advance in the management of those difficult cases of asthma that are particularly resistant to typical treatment modalities. In this review article, we intend to address the potential role of TNF-alpha in asthma and to put forward the idea that drugs that have been developed to neutralize the deleterious effects of TNF-alpha may also be useful in the management of chronic severe asthma.