Effects of dexamethasone on antigen-induced airway eosinophilia and M-2 receptor dysfunction

In antigen-challenged guinea pigs, airway hyperreactivity is due to recruit ment of eosinophils to the airway nerves and dysfunction of M-2 muscarinic receptors. M-2 receptor dysfunction is caused by eosinophil major basic pro tein, which is an allosteric antagonist at the receptor. Because glucocorti coids inhibit airway hyperreactivity in humans and in animal models of asth ma, we tested whether dexamethasone treatment (6 mug.kg(-1).d(-1) for 3 d, intraperitoneal) before antigen challenge prevents M-2 receptor dysfunction and airway hyperreactivity. Guinea pigs were sensitized to ovalbumin via i ntraperitoneal injections, and were challenged with ovalbumin via inhalatio n. Twenty-four hours later, hyperreactivity and Mt receptor function were t ested. Antigen-challenged animals were hyperreactive to vagal stimulation, and demonstrated loss of M-2 receptor function. Dexamethasone pretreatment prevented hyperreactivity and M-2 receptor dysfunction in antigen-challenge d guinea pigs. Antigen challenge resulted in recruitment of eosinophils to the airways and to the airway nerves. Dexamethasone prevented recruitment o f eosinophils to the airway nerves but did not affect total eosinophil infl ux into the airways. These results demonstrate that dexamethasone prevents antigen-induced hyperreactivity by protecting neuronal M-2 muscarinic recep tors from antagonism by eosinophil major basic protein, and this protective mechanism appears to be by specifically inhibiting eosinophil recruitment to the airway nerves.