Comparison of cough reflex sensitivity after an inhaled antigen challenge between actively and passively sensitized guinea pigs

Johsuke Hara,Miki Abo,Kouichi Nobata,Yoshitaka Oribe,Yoriko Herai,Shiho Furusho,Nobuyuki Katayama,Masaki Fujimura,Kazuo Kasahara,Toshiyuki Kita,Akihiro Hori,Noriyuki Ohkura,Masahide Yasui,Yoshihisa Ishiura,Haruhiko Ogawa,Shinji Nakao,Shigeharu Myou

doi:10.1186/1745-9974-1-6

Abstract

BackgroundLate asthmatic response is observed following antigen challenge in actively, but not passively, sensitized guinea pigs. Although cough reflex sensitivity is increased after antigen challenge in actively sensitized guinea pigs, it is unknown whether the antigen-induced increase in cough reflex sensitivity develops in passively sensitized animals. The aim of this study was to compare the cough reflex sensitivity to inhaled capsaicin after an inhaled antigen challenge between actively and passively sensitized guinea pigs.MethodsMeasurement of number of coughs elicited by increasing concentrations of capsaicin (10-6 and 10-4 M) and bronchial responsiveness to ascending concentrations of methacholine, and analysis of bronchoalveolar lavage fluid (BALF) were separately performed 24 h after an antigen challenge in actively and passively sensitized guinea pigs.ResultsPercentage of eosinophils in BALF and bronchial responsiveness to methacholine were increased 24 h after the antigen challenge in both actively and passively sensitized animals compared with saline-challenged actively and passively sensitized animals, respectively. Absolute number of eosinophils in BALF from actively sensitized and antigen-challenged guinea pigs was significantly greater than that from passively sensitized and antigen-challenged animals. Cough response to capsaicin and concentration of substance P in BALF were increased 24 h after the antigen challenge in actively sensitized guinea pigs, but not in passively sensitized guinea pigs. Bronchial responsiveness, cough reflex sensitivity and substance P concentration and total cells in BALF were increased in actively sensitized and saline challenged guinea pigs compared with passively sensitized and saline challenged animals.ConclusionThe results suggest that active sensitization per se increases cough reflex sensitivity accompanied by increased inflammatory cells and substance P level in BALF, and antigen challenge further increases them, while simple IgE- and/or IgG-mediated allergic reaction per se or the low intensity of eosinophil infiltration in the airway itself may not affect cough reflex sensitivity in guinea pigs.

Highlights

Late asthmatic response is observed following antigen challenge in actively, but not passively, sensitized guinea pigs
We have shown in actively sensitized guinea pigs that cough reflex sensitivity is increased 24 h after an inhaled antigen challenge, which is not mediated by bronchoconstriction [4]
Allergic reaction and cough hypersensitivity may be induced by chemical mediators such as histamine [5], prostaglandins [6], thromboxane A2 (TXA2) [4], and platelet activating factor (PAF), which are released from mast cells activated by IgE antibody and/or production of Th2 cytokines [7] such as IL-4, IL-5 and IL-13

Summary

Introduction

Late asthmatic response is observed following antigen challenge in actively, but not passively, sensitized guinea pigs. Chronic cough is a common and distressing symptom Eosinophilic airway disorders such as eosinophilic bronchitis without asthma [1] and atopic cough [2] are important causes of the chronic cough. In these disorders, cough reflex sensitivity is heightened while patients are coughing and becomes normal on successful treatment [3]. Simple IgE- and/or IgG-mediated allergic airway reaction occurs when passively sensitized guinea pigs are challenged with an aerosolized antigen. It is, unknown whether the simple IgE- and/or IgG-mediated allergic airway reaction can increase cough reflex sensitivity. We compared the cough reflex sensitivity to inhaled capsaicin after an inhaled antigen challenge between actively and passively sensitized guinea pigs

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