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Etanercept prevents airway hyperresponsiveness by protecting neuronal M2 muscarinic receptors in antigen‐challenged guinea pigs

Background and purpose:  Increased tumour necrosis factor‐α (TNF‐α) is associated with airway hyperreactivity in antigen‐challenged animals. In human asthmatics, TNF‐α is increased and blocking it prevents airway hyperreactivity in some asthmatic patients. However, the mechanisms by which TNF‐α mediates hyperreactivity are unknown. Airway hyperreactivity can be caused by dysfunction of neuronal M2 muscarinic receptors that normally limit acetylcholine release from parasympathetic nerves. Here we test whether blocking TNF‐α receptors with etanercept prevents M2 receptor dysfunction and airway hyperreactivity in antigen‐challenged guinea pigs.