Anti-TNF-α and Th1 cytokine-directed therapies for the treatment of asthma

Abstract

This article examines recent work about the role of TNF-alpha and of selected Th1-related cytokines in asthma with particular emphasis on the therapeutic potential of blocking the biological activity of these mediators. Current research endeavours suggest that asthma pathogenesis is driven by a mixed Th1/Th2 immune response. The contribution of individual Th1-associated and Th2-associated effector mechanisms to this mixed response profile is highly heterogeneous and variations in response patterns seem to be associated with heterogeneity in clinical phenotypes. In particular, it is now acknowledged that allergen-specific Th1 responses appear to be responsible for the pathogenetic effects seen in patients suffering from the more severe chronic forms of the disease. This is important because usual treatments for asthma appear to have limited effects on the more chronic severe forms of the disease and there is a pressing need for the development of new treatment strategies. The failure of topical corticosteroids to reduce TNF-alpha and Th1-derived cytokines to a significant level in asthmatic airways may explain to a certain extent why these drugs appear to have limited effects in the more severe forms of asthma. It is likely that therapies blocking TNF-alpha and interfering with Th1-derived cytokines may be a considerable advance in the management of those asthma patients who are particularly resistant to typical treatment modalities.