[A guinea pig model of respiratory syncytial virus infection for cough and its neurogenic inflammatory mechanism].

OBJECTIVE: To establish a guinea pig model of acute and postinfectious cough caused by respiratory syncytial virus (RSV) infection and investigate the role of neurogenic inflammation in its pathogenesis. METHODS: Fifty guinea pigs were randomly divided into control group and four groups of Days 6, 12, 28 and 42 after RSV inoculation (n = 10 each). The RSV suspension was inoculated by intranasal instillation. Buxco system was used to assess the cough reflex sensitivity (CRS) to inhaled capsaicin. Airway inflammation was determined by bronchoalveolar lavage fluid (BALF) cytology and lung histopathology. RSV antigen and nucleic acid were detected by immunofluorescence and real-time fluorescence quantitative PCR (polymerase chain reaction). After modeling, the content of substance P in homogenate of lung tissue was detected by ELISA (enzyme-linked immunosorbent assay) kit. The level of neurokinins receptor 1 (NK1) mRNA in lung tissue was detected by real-time PCR. The expression of substance P protein in lung tissue was detected by immunohistochemistry. The correlation analyses between CRS and the levels of substance P and NK1 mRNA were performed respectively. RESULTS: The viral antigen expression could be found in lung tissue of RSV infected guinea pigs. The concentration of RSV RNA content showed a gradually decreasing trend with infection time until 42 days at very low titers. The CRS values were (8.0 ± 1.2), (8.7 ± 2.0), (7.6 ± 1.4) and (6.7 ± 1.2) cough counts at Days 6, 12, 28 and 42 respectively. Compared with (2.5 ± 0.5) cough counts of control group, the CRS to capsaicin increased significantly in all animals with PIV3 inoculation (all P < 0.05) and peaked at Day 12 (P < 0.01). BALF cytology and lung tissue pathology showed airway inflammation during the acute stage of infection without pneumonia. All the contents of substance P in lung tissue homogenates increased markedly in infected groups. The immunohistochemical results of substance P in lung tissue of infected groups showed a distinct brown-yellow positive expression. In addition to Group Day 6, the NK1 mRNA contents of lung tissue in all other infection groups became elevated significantly. The correlation analysis showed a positive correlation between CRS and the levels of substance P and NK1 mRNA (all P < 0.05). CONCLUSION: A guinea pig model for cough of RSV infection has been successfully established. The elevated releases of substance P and its receptor may cause neurogenic inflammation. And airway neurogenic inflammation may play a decisive role in the heightened CRS and postinfectious cough induced by RSV.

[A guinea pig model of parainfluenza virus type 3 infection-induced acute and postinfectious cough].

OBJECTIVE: To establish a guinea pig model of cough induced by human parainfluenza virus type 3 (PIV3) infection, and to investigate the change of the cough reflex sensitivity (CRS). METHODS: Sixty male SPF guinea pigs were divided into 6 groups (n=10, each), namely, a normal control group, an asthma group and 4 groups of PIV3 inoculation which included post-infection day (PID) 6, 12, 28, and 42. Infected animals were inoculated by intranasal instillation of PIV3 suspension. Control animals were inoculated by uninfected cell culture medium. Asthma animals were sensitized and challenged by ovalbumin. The Buxco system was used to assess cough reflex sensitivity (CRS) elicited by capsaicin and airway hyper-reaction (AHR). Airway inflammation was studied by bronchoalveolar lavage (BAL) cytology and lung histopathology. RESULTS: The CRS of PID 6, 12, 28 and 42 groups was 7.50 (5.25), 7.30 (7.25), 8.40 (9.75) and 8.20 (5.50) Cough counts (CCnt). Compared with 2.50 (3.00) CCnt of the vehicle group, the CRS to capsaicin increased significantly in all the animals with PIV3 inoculation (P value were 0.024, 0.03, 0.011 and 0.008) and peaked in PID 42. There was no significant difference (P=0.18) between 3.90 (1.75) CCnt of the asthma animals and the normal control. Animals of PID 6 showed significantly greater AHR to 2 highest concentrations of methacholine than the normal controls. BAL total cell counts of both the PIV3-inoculated and the asthma animals were significantly higher than those of the normal control, with the number of lymphocytes increased significantly within first 2 weeks after PIV3 inoculation. The lung pathology of PIV3-inoculated animals showed airway inflammation without pneumonia in acute infectious phase. CONCLUSIONS: An animal model of cough induced by PIV3 was created. The CRS of infected guinea pigs increased significantly in both acute and subacute phases of cough. Elevation of CRS may be characteristic of cough caused by virus.