Virus-induced airway inflammation and hyperresponsiveness in the guinea-pig is inhibited by levodropropizine.
Intratracheal Parainfluenza type 3 (PI-3) virus inoculation of guinea pigs leads to a non-specific airway hyperresponsiveness in vivo and in vitro which coincides with a significant increase in the number of inflammatory cells in the broncho-alveolar lavage fluid (90% increase, 4 days after inoculation). The activity of the bronchoalveolar cells, as measured by the chemiluminescence production of infected animals is significantly diminished (34.2%, 4 days after inoculation) after renewed stimulation with PI-3 virus in vitro as compared to the chemiluminescence production by bronchoalveolar cells obtained from control guinea pigs. Pretreatment of the guinea-pigs with the antitussive agent levodropropizine, administered intra-peritoneally twice a day for five successive days at a dose of 10 mg/kg, prevents the virus-induced airway hyperresponsiveness in vivo and in vitro, and inhibits the influx of broncho-alveolar cells. Levodropropizine at a dose of 1 mg/kg did not modulate these responses. Further, the decrease in chemiluminescence production of broncho-alveolar cells obtained from virus-infected animals after PI-3 virus stimulation in vitro was inhibited by levodropropizine (10 mg/kg). These data demonstrate the ability of levodropropizine to counteract the hyperresponsiveness phenomenon and the associated inflammatory event induced by PI-3 virus, an effect which may be due to its capacity to act on the peptidergic system or may be due to the anti-allergic/bronchoconstrictor property of this compound.
Folkerts
G
G
Department of Pharmacology, Faculty of Pharmacy, Utrecht University, The Netherlands.
van der Linde
H J
HJ
Omini
C
C
Nijkamp
F P
FP
D000818:Animals; D000996:Antitussive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D016535:Bronchial Hyperreactivity / Q000382:microbiology / Q000517:prevention & control*; D001991:Bronchitis / Q000382:microbiology / Q000517:prevention & control*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004195:Disease Models, Animal; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D010224:Parainfluenza Virus 3, Human; D018184:Paramyxoviridae Infections / Q000517:prevention & control*; D011292:Premedication; D011409:Propylene Glycols / Q000008:administration & dosage / Q000627:therapeutic use*; D013047:Specific Pathogen-Free Organisms
D000996:Antitussive Agents; D011409:Propylene Glycols; D016210:Methacholine Chloride; D006632:Histamine; C035916:dipropizine