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Sensory neuropeptides are not directly involved in bronchial hyperresponsiveness induced by interleukin‐8 in guinea‐pigsin vivo

机译:Sensory neuropeptides are not directly involved in bronchial hyperresponsiveness induced by interleukin‐8 in guinea‐pigsin vivo

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SummaryBackgroundInterleukin‐8 (IL‐8) hus been shown to be a chemotactic factor for netitrophils, T‐lymphocytes and eosinophils. Repeated intranasal administration of IL‐8 enhances bronchial responsiveness to inhaled histamine in guinea‐pigs. Neuropeptides which arc released trotn C‐fibre nerve‐endings have been postulated to induce bronchial hyperresponsiveness through neurogenic inflammation.ObjectiveThis study was conducted to examine whether sensory neuropeptides are involved in the IL‐8‐induced bronchial hyperresponsiveness.MethodsIL‐8 at a dose of 5μg/kg was administered intranasally to guinea‐pigs twice a week for 3 weeks. One day after the last administration, animals were anesthetized and artificially ventilaled through tracheal cannula, and lateral pressure at the tracheal cannula (Pao) was measured as an overall index of airway responses lo increasing concentrations of inhaled histamine (25, 50, 100, and 200 μg/mL). A NKI and NK2 dual antagonist FK224(10mg/kg), a selective NK1 antgonist FK888 (10mg/kg) or vehicle was intravenously administered 10min before measurement of bronchial responsiveness.ResultThe IL‐8 treatment significantly enhanced bronchial responsiveness to histamine (ANOVAP<0.01). FK224 or FK888 did not alter the IL‐8‐induced bronchial hyperresponsiveness.ConclusionWe conclude that repeated intranasal administratioti of IL‐8 causes bronchial hyperresponsiveness (BHR) and that neuropeptides such as neurokinin A and substance P do not directly contribute to the dev

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