Fujimura M, Tsujiura M, Nomura M, Mizuguchi M, Matsuda T, Matsushima K
Third Department of Internal Medicine, Kanazawa University School of Medicine, Japan.
Clin Exp Allergy. 1996 Mar;26(3):357-62.
Interleukin-8 (IL-8) has been shown to be a chemotactic factor for neutrophils, T-lymphocytes and eosinophils. Repeated intranasal administration of IL-8 enhances bronchial responsiveness to inhaled histamine in guinea-pigs. Neuropeptides which are released from C-fibre nerve-endings have been postulated to induce bronchial hyperresponsiveness through neurogenic inflammation.
This study was conducted to examine whether sensory neuropeptides are involved in the IL-8-induced bronchial hyperresponsiveness.
IL-8 at a dose of 5 micrograms/kg was administered intranasally to guinea-pigs twice a week for 3 weeks. One day after the last administration, animals were anesthetized and artificially ventilated through tracheal cannula, and lateral pressure at the tracheal cannula (Pao) was measured as an overall index of airway responses to increasing concentrations of inhaled histamine (25, 50, 100, and 200 micrograms/mL). A NK1 and NK2 dual antagonist FK224 (10 mg/kg), a selective NK1 antagonist FK888 (10 mg/kg) or vehicle was intravenously administered 10 min before measurement of bronchial responsiveness.
The IL-8 treatment significantly enhanced bronchial responsiveness to histamine (ANOVA P < 0.01). FK224 or FK888 did not alter the IL-8-induced bronchial hyperresponsiveness.
We conclude that repeated intranasal administration of IL-8 causes bronchial hyperresponsiveness (BHR) and that neuropeptides such as neurokinin A and substance P do not directly contribute to the development of BHR induced by IL-8.
白细胞介素-8（IL-8）已被证明是中性粒细胞、T淋巴细胞和嗜酸性粒细胞的趋化因子。在豚鼠中，反复经鼻给予IL-8可增强支气管对吸入组胺的反应性。据推测，从C纤维神经末梢释放的神经肽可通过神经源性炎症诱导支气管高反应性。
本研究旨在探讨感觉神经肽是否参与IL-8诱导的支气管高反应性。
以5微克/千克的剂量每周两次经鼻给予豚鼠IL-8，共3周。末次给药后1天，将动物麻醉并通过气管插管进行人工通气，测量气管插管处的侧压（Pao），作为气道对递增浓度吸入组胺（25、50、100和200微克/毫升）反应的总体指标。在测量支气管反应性前10分钟静脉注射NK1和NK2双重拮抗剂FK224（10毫克/千克）、选择性NK1拮抗剂FK888（10毫克/千克）或赋形剂。
IL-8治疗显著增强了支气管对组胺的反应性（方差分析P<0.01）。FK224或FK888未改变IL-8诱导的支气管高反应性。
我们得出结论，反复经鼻给予IL-8可导致支气管高反应性（BHR），并且神经激肽A和P物质等神经肽并不直接促成IL--8诱导的BHR的发展。
