Tumor necrosis factor inhibitors for the treatment of asthma

Asthma is a unique form of chronic airway inflammation characterized by reversible airway obstruction, airway hyperresponsiveness and the production of specific inflammatory mediators. Local activation of both immune and nonimmune cells in the lung triggers the release of these immunomodulator molecules. Among them, tumor necrosis factor (TNF)-alpha, a multipotent pro-inflammatory mediator, plays a critical role in immunoregulation of asthma by contributing to bronchopulmonary inflammation and airway hyperresponsiveness. Blocking TNF-alpha activity has already shown outstanding efficacy in other chronic inflammatory diseases including rheumatoid arthritis, Crohn's disease, and psoriasis. The successful treatment of these other chronic inflammatory diseases provides hope that TNF inhibitors may have application for the treatment of asthma. Recent developments in animal models and clinical trials in patients with severe asthma provide strong support for the concept that blocking TNF-alpha activity represents a new approach in asthma therapy. In this review, we address the multipotential role of TNF-alpha in asthma and the efficacy and safety of TNF-alpha blocking agents in asthma.