Virus‐induced airway hyperresponsiveness in the guinea‐pig: possible involvement of histamine and inflammatory cells

Abstract

1 Guinea-pig tracheal contractions by histamine and by the cholinoceptor agonist, arecoline, are significantly enhanced (30% and 20%, respectively), 96 h after intra-tracheal inoculation with Parainfluenza-3 (PI-3) virus. 2 The airway hyperresponsiveness in animals inoculated with virus coincides with a significant increase in the number of broncho-alveolar cells (82%), and in the albumin concentration (121%) in lung lavage fluid, relative to values obtained in guinea-pigs challenged with control solution. 3 The chemiluminescence production by isolated broncho-alveolar cells, obtained from virus-infected guinea-pigs 96 h after inoculation stimulated with PI-3 virus in vitro, is significantly reduced by 42% relative to broncho-alveolar cells obtained from animals inoculated with control solution. This diminution was not specific for stimulation by PI-3 virus since the chemiluminescence production was also significantly reduced by 30% in response to zymosan. 4 Pretreatment of the guinea-pigs with the anti-allergic drugs, oxatomide (2.5 mg kg-') or nedocromil (2.5 mg kg-'), or the specific HI-histamine receptor antagonist, levocabastine (0.25 mg kg-'), administered intra-peritoneally twice a day for five successive days, inhibits the virus-induced airway hyperresponsiveness, suppresses the influx of broncho-alveolar cells and increase in albumin content, and corrects the reduced chemiluminescence production by broncho-alveolar cells in response to zymosan. 5 In contrast, the cyclo-oxygenase inhibitor, suprofen (5.0 mg kg-1), the 5-HT2 receptor antagonist, ketanserin (0.63 mg kg-'), or the Ca2" overload blocker, flunarizine (2.5 mg kg-') do not modify the above mentioned processes. 6 The platelet-activating factor receptor antagonist, WEB 2170 (10 mg kg-'), reduces virus-induced airway hyperresponsiveness and influx of broncho-alveolar cells into the lungs but does not attenuate the increase of albumin in the bronchial lavage fluid. 7 Guinea-pigs nebulized with histamine, twice a day (30 min) during 4 successive days, do not demonstrate an increased airway responsiveness, but instead show tachyphylaxis in response to histamine in vitro. In addition, no influx of inflammatory cells is found in these animals. 8 These results suggest that histamine does not directly increase the responsiveness of the guinea-pig trachea; however, histamine may be involved in a cascade of events leading to airway hyperresponsiveness after a viral infection, a process that could be related to an influx and/or an activation of broncho-alveolar cells after PI-3 virus stimulation.

Virus-induced airway hyperresponsiveness in guinea pigs is related to a deficiency in nitric oxide.

“…In patients infected with respiratory syncytial virus, the release of histamine in nasopharyngeal secretions was detected significantly more often and in higher concentrations in patients with wheezing (37). Histamine concentrations are increased in the broncho-alveolar lavage fluid of PI-3 virus-treated guinea pigs (6) and antiallergic drugs and antihistamines can prevent the virus-induced airway hyperresponsiveness and influx of inflammatory cells (27). Therefore, a number of processes may act additively or synergistically during the development of airway hyperresponsiveness.…”

Potentiation by viral respiratory infection of ovalbumin‐induced guinea‐pig tracheal hyperresponsiveness: role for tachykinins

“…Growth medium was treated identically. Previous experiments have shown that PI-3 virus could be isolated from the airways of all guinea-pigs 2 days after infection (Folkerts et al, 1993a).…”

Role of Rho-Associated Protein Kinase and Histamine in Lysophosphatidic Acid-Induced Airway Hyperresponsiveness in Guinea Pigs

“…On the other hand, Santing et al (23) described the contribution of histamine to the development of the late asthmatic reaction as well as to early and late bronchial hyperreactivity. Histamine does not directly increase the responsiveness of guinea pig trachea; however, histamine may be involved in a cascade of events leading to airway hyperresponsiveness (24). Although a clear explanation has not been reported regarding the involvement of histamine in the development of airway hyperresponsiveness, the present study indicates that histamine contributes to LPA-induced airway hyperresponsiveness based on the effectiveness of antihistaminics and the in vitro experiment.…”