The therapeutic effects of labetalol in chronic stress- and immuno-agonist-induced cough hypersensitivity and lung inflammation involve reducing interferon-γ-producing T lymphocytes.

Background: Psychological stress correlates with chronic cough, which is often triggered by respiratory viruses. Chronic stress promotes sympathetic nerves to release norepinephrine and neuropeptide Y. Labetalol blocks sympathetic adrenergic receptors. Norepinephrine and neuropeptide Y can upregulate interferon-γ (IFN-γ)-producing lymphocytes and increase IFN-γ levels Methods: We investigated the effects and underlying mechanisms of labetalol on chronic stress and immuno-agonist-induced cough hypersensitivity and lung inflammation. Results: Chronic stress and immuno-agonists induced cough hypersensitivity and pulmonary inflammation in guinea pigs, which were alleviated by labetalol. In mice, chronic stress triggered the release of norepinephrine and neuropeptide Y, leading to IFN-γ-producing T lymphocytosis and pulmonary inflammation. Additionally, chronic stress and immuno-agonists increased IFN-γ in the lung of guinea pigs and mice. Labetalol effectively reduced chronic stress-induced and immuno-agonist-induced IFN-γ-producing T lymphocytosis and lung inflammation in mice. Labetalol dose-dependently inhibited the increase in IFN-γ-producing T lymphocytes induced by immuno-agonists and norepinephrine Conclusions: Chronic stress can stimulate the release of sympathetic neurotransmitters, which may increase IFN-γ-producing T lymphocytes and lead to cough hypersensitivity and pulmonary inflammation by activating the adrenergic receptors. Immuno-agonists may increase IFN-γ-producing T lymphocytes, exacerbating chronic stress-induced cough hypersensitivity and pulmonary inflammation. The therapeutic effects of labetalol in chronic stress and immuno-agonist-induced cough hypersensitivity and pulmonary inflammation possibly occur by reducing IFN-γ-producing T lymphocytes.