IFN-γ Enhances the Cough Reflex Sensitivity via Calcium Influx in Vagal Sensory Neurons

Rationale: Cough hypersensitivity syndrome is often triggered by a viral infection. The viral infection might trigger cough hypersensitivity via increasing the release of IFN-γ from T lymphocytes in the lung.Objectives: To investigate effects of IFN-γ on the vagal sensory neurons and the cough reflex.Methods: Effects of IFN-γ on the cough reflex were investigated in guinea pigs. Cellular immunofluorescence imaging, calcium imaging, and patch clamp techniques were used to study effects of IFN-γ in primary cultured rat vagal sensory neurons.Measurements and Main Results: Intratracheal instillation of IFN-γ enhanced the cough response to citric acid in vivo. IFN-γ significantly increased levels of phosphorylated signal transducer and activator of transcription-1 but not phosphorylated transient receptor potential vanilloid 1 in vitro. Not only did IFN-γ enhance the response of neurons to capsaicin and electric stimulation, but also it directly induced Ca2+ influx, membrane depolarization, and action potentia...