IL-1β: a key modulator in asthmatic airway smooth muscle hyper-reactivity

Asthma is a chronic inflammatory disorder of the airway. It is characterized by airway hyper-reactivity, which can be attributed to the chronically inflamed airway. However, the molecular mechanism is still under investigation. In this article, we have shown that IL-1 beta is a key molecule that can orchestrate both Toll-like receptor and muscarinic receptor pathways, and that antagonizing the function of IL-1 beta has a promising future as a potential drug target for asthma treatment. IL-1 beta can activate NF-kappa B pathways via Toll-like receptors, and NF-kappa B will eventually transactivate the genes of cytokines, chemokines, proteins of the complement system, adhesion molecules and immune receptors involved in inflammation. IL-1 beta can activate eosinophils, which can release major basic protein (MBP) to antagonize the M-2 receptors leading to excessive acetylcholine release. Acetylcholine has an effect on M-3 receptors, which are related to airway smooth muscle contraction and mucus production. IL-1 beta is reported to activate COX-2 resulting in heterologous desensitization of adenylate cyclase and impairs relaxation of the ASM. IL-1 beta is involved in mediation of neutrophilic inflammation. Identification of the prominent role of IL-1 beta in asthma could lead to successful use of anti-IL1 beta agents.