Tumour necrosis factor-α (TNF-α) plays a relevant role in many features of asthma pathobiology by exerting its effects on both airway inflammatory and structural cells (Fig. 7.1) [1]. This pleiotropic cytokine is produced by several cell types including Th1 lymphocytes, macrophages and mast cells and induces the recruitment of neutrophils and eosinophils into the airways via up-regulation of epithelial and endothelial adhesion molecules [2, 3]. Moreover, by enhancing TGF-β expression, TNF-α stimulates airway smooth muscle cell proliferation, as well as fibroblast growth and maturation into myofibroblasts [4–6]. Therefore, TNF-α can contribute to the development of severe asthma not only by inducing airway inflammation and hyperresponsiveness but also by promoting bronchial remodelling [7]. Indeed, TNF-α is overexpressed in the airways of patients with severe asthma and also directly stimulates airway smooth muscle contraction through changes in intracellular calcium fluxes [1].