ROLE OF SENSORY NEUROPEPTIDES IN PIV-3-INFECTION-INDUCED AIRWAY HYPERRESPONSIVENESS IN GUINEA-PIGS

Viral respiratory tract infections are known to induce transient airwa y hyperresponsiveness. The role of the nonadrenergic noncholinergic ne uropeptide system on virus-induced airway hyperresponsiveness was stud ied in the guinea pig. Ten guinea pigs were inoculated with parainflue nza 3 virus (PIV-3, 2 x 10(6) PFU) by nasal route, 16 animals served a s untreated controls. Viral infection was proven by histological chang es and by demonstration of viral antigen using immunohistochemical tec hniques. Four days after inoculation, airway responsiveness to inhaled acetylcholine (ACH) aerosol was measured in anesthetized and tracheot omized guinea pigs. The ACH concentration which produced an increase o f 100% in pulmonary resistance (PC100 RI) and in dynamic elastance (PC 100 (Edyn)) was calculated from a 5-step ACH dose-response curve (0.12 5, 0.25, 0.5, 1.0 and 2.0% ACH). Two further groups of 8 PIV-3-infecte d guinea pigs and 8 noninfected control animals were pretreated with c apsaicin in increasing doses (50, 100, 125 and 150 mg/kg) on 4 consecu tive days starting 6 days before virus inoculation. Measurements of ai rway responsiveness to ACH were performed 4 days after virus inoculati on. Another 5 uninfected control animals were pretreated only with the solvent for capsaicin and inoculated with virus-free cell supernatant . PIV-3 infection increased airway responsiveness to ACH compared to n oninfected 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-pr etreated PIV-3-infected animals, airway hyperresponsiveness was comple tely prevented compared to the virus-infected group without capsaicin pretreatment (PC100 RI > 2.0 vs. 0.81% ACH, p < 0.01; PC100 (Edyn) 1.4 2 vs. 0.52% ACH, p < 0.01). As neuropeptide depletion with capsaicin c ompletely prevented the increase in airway constrictory response to AC H following virus infection, we conclude that neuropeptides are effect ively involved in PIV-3-induced airway hyperresponsiveness in the guin ea pig.