Immediate anaphylactic bronchoconstriction induces airway hyperreactivity in anaesthetized guinea‐pigs

Abstract

1 The possible acute occurrence of airway hyperreactivity after immediate-type bronchial anaphylaxis has been investigated in anaesthetized guinea-pigs actively sensitized to ovalbumin (OA). 2 Aerosol challenge (OA 10 mgml-1, 5s) provoked immediate bronchoconstriction which was substantially, although incompletely, reversed by isoprenaline (Iso) infusion (1 ,igkg1 min 1) for 10 min). 3 Bronchoconstrictor responses to 5-hydroxytryptamine (5-HT) were enhanced in challenged animals when compared to those in non-challenged animals that had also received Iso. This was seen as a leftward shift in the location of the dose-response curve for the bronchoconstrictor effect of 5-HT (dose-ratio 2.45, 95% confidence limits 1.77-3.38; P < 0.01). This phenomenon was associated with pulmonary infiltration of polymorphonuclear leukocytes, which was not modified by Iso treatment.4 Iso infusion alone caused a slight enhancement of airway reactivity seen as a small leftward shift of the dose-response curve for the bronchoconstrictor effect of 5-HT (dose-ratio 1.51, 95% confidence limits 1.07-2.13; P < 0.05). 5 These results support a causal relationship between acute pulmonary inflammation and airway hyperreactivity in an animal model of human allergic asthma.

Effects of bradykinin receptor antagonists on antigen‐induced respiratory distress, airway hyperresponsiveness and eosinophilia in guinea‐pigs

“…These experiments confirm previous studies demonstrating airway hyperresponsiveness to bronchoconstrictors in sensitized guinea-pigs after a single challenge (Daffonchio et al, 1988;1989;Seeds et al, 1991), or repeated challenges (Ishida et al, 1989;Schellenberg et al, 1991) 1988; Hutson et al, 1988;Richards et al, 1989;Seeds et al, 1991) and chronic (Ishida et al, 1989; exposure to antigen has been reported.…”

“…In the single challenge study, guinea-pigs were also hyperresponsive to the bronchoconstrictor action of histamine. Moreover, hyperresponsiveness to ACh and 5-HT has been reported under similar experimental conditions (Daffonchio et al, 1988;1989). It is feasible then, that the airways were also hyperresponsive to mast cell mediators released endogenously by inhaled antigen.…”

Temporal relationships between leukocytes, IL-5 and IL-8 in guinea pig lungs, plasma cortisol and airway function after antigen challenge

“…Eosinophils appeared in the BALF from about 6 h. Thus, in common with other studies using both conscious [21,26] and anaesthetized [2,27] guinea pigs, the increase in responsiveness occurred long before the appearance of eosinophils in BALF. These observations would seem to dissociate the development of airway hyperresponsiveness from leukocyte infiltration.…”

“…Administering inhaled antigen to the sensitised animal can lead to the development of a number of features in common with bronchial asthma including: early and late phase bronchoconstrictor responses, inflammatory cell recruitment and the development of airway hyperreactivity [2][3][4][5][6][7]. Knowledge of the mechanisms underlying these inflammatory events in guinea pigs is growing with development of cytokine-specific antagonists [8][9][10][11][12][13] and the use of antibodies directed against several of the cellular adhesion molecules [14][15][16].…”

“…Others have also demonstrated airway hyperreactivity at the time of the late phase [21] and there are studies which show AHR as early as 1 h after the antigen challenge [2]. However, there are few studies which have followed the time course of airway function, cell influx, airway hyperresponsiveness and release of the cytokines IL-5 and IL-8 into lavage fluid in the same animal model.…”