Riedel F, Benden C, Philippou S, Streckert H J, Marek W
Department of Pediatrics, Ruhr University Bochum, Germany.
Respiration. 1997;64(3):211-9. doi: 10.1159/000196673.
Viral respiratory tract infections are known to induce transient airway hyper-responsiveness. The role of the nonadrenergic noncholinergic neuropeptide system on virus-induced airway hyperresponsiveness was studied in the guinea pig. Ten guinea pigs were inoculated with parainfluenza 3 virus (PIV-3.2 x 10(6) PFU) by nasal route. 16 animals served as untreated controls. Viral infection was proven by histological changes and by demonstration of viral antigen using immunohistochemical techniques. Four days after inoculation, airway responsiveness to inhaled acetylcholine (ACH) aerosol was measured in anesthetized and tracheotomized guinea pigs. The ACH concentration which produced an increase of 100% in pulmonary resistance (PC100 RI) and in dynamic elastance (PC100 Edyn) was calculated from a 5-step ACH dose-response curve (0.125, 0.25, 0.5, 1.0 and 2.0% ACH). Two further groups of 8 PIV-3-infected guinea pigs and 8 noninfected control animals were pretreated with capsaicin in increasing doses (50, 100, 125 and 150 mg/kg) on 4 consecutive days starting 6 days before virus inoculation. Measurements of airway responsiveness to ACH were performed 4 days after virus inoculation. Another 5 uninfected control animals were pretreated only with the solvent for capsaicin and inoculated with virus-free cell supermatant. PIV-3 infection increased airway responsiveness to ACH compared to noninfected controls [PC100 RI 0.81 vs. > 2.0% ACH (median). p < 0.002 PC100 Edyn 0.52 vs. 1.07% ACH (median), p < 0.01]. In capsaicin-pretreated PIV-3-infected animals, airway hyperresponsiveness was completely prevented compared to the virus-infected group without capsaicin pretreatment (PC100 RI > 2.0 vs. 0.81% ACH, p < 0.01; PC100 Edyn 1.42 vs. 0.52% ACH p < 0.01). As neuropeptide depletion with capsaicin completely prevented the increase in airway constrictory response to ACH following virus infection, we conclude that neuropeptides are effectively involved in PIV-3-induced airway hyperresponsiveness in the guinea pig.
已知病毒性呼吸道感染会诱发短暂性气道高反应性。在豚鼠中研究了非肾上腺素能非胆碱能神经肽系统在病毒诱导的气道高反应性中的作用。10只豚鼠经鼻接种副流感3病毒（PIV - 3，2×10⁶ PFU）。16只动物作为未处理的对照。通过组织学变化和使用免疫组化技术证明病毒抗原来证实病毒感染。接种后4天，在麻醉并气管切开的豚鼠中测量气道对吸入乙酰胆碱（ACH）气雾剂的反应性。从5步ACH剂量反应曲线（0.125%、0.25%、0.5%、1.0%和2.0% ACH）计算出使肺阻力（PC100 RI）和动态弹性（PC100 Edyn）增加100%的ACH浓度。另外两组，每组8只PIV - 3感染的豚鼠和8只未感染的对照动物，在病毒接种前6天开始连续4天用递增剂量（50、100、125和150 mg/kg）的辣椒素预处理。在病毒接种后4天测量气道对ACH的反应性。另外5只未感染的对照动物仅用辣椒素溶剂预处理并接种无病毒的细胞上清液。与未感染的对照相比，PIV - 3感染增加了气道对ACH的反应性[PC100 RI 0.81 vs. >2.0% ACH（中位数），p <0.002；PC100 Edyn 0.52 vs. 1.07% ACH（中位数），p <0.01]。与未用辣椒素预处理的病毒感染组相比，在经辣椒素预处理的PIV - 3感染动物中，气道高反应性被完全预防（PC100 RI >2.0 vs. 0.81% ACH，p <0.01；PC100 Edyn 1.42 vs. 0.52% ACH，p <0.01）。由于用辣椒素耗尽神经肽完全预防了病毒感染后气道对ACH收缩反应的增加，我们得出结论，神经肽有效地参与了豚鼠中PIV - 3诱导的气道高反应性。
