Time course of pharmacological modulation of peak eosinophilic airway inflammation after mite challenge in guinea pigs: A therapeutic approach

Background: It is well known that eosinophilic airway inflammation develops after allergen challenge in sensitized humans and animals. However, the de tailed time course of suppression of early eosinophilic airway inflammation by pharmacological agents given just after challenge has not been discusse d. Therefore, we aimed to evaluate the time course relationship of the supp ression of peak eosinophilia by anti-cytokines and pharmacological agents g iven several hours after the aerosol challenge by a therapeutic approach. M ethods: We used crude mite extract as an allergen to create a sensitization and inhalation challenge, and performed bronchoalveolar lavages (BAL) afte r the inhalation challenge to observe the degree of eosinophilic airway inf lammation in guinea pigs. Various anti-cytokines (anti-IL-3 and anti-IL-5) and pharmacological agents (dexamethasone, theophylline, and roxithromycin) were given within several hours after the acute aeorosol challenge to eval uate the suppressive effect on peak eosinophilia in BAL fluid, which occurr ed 24 h after the challenge. Results: Our results show that anti-IL-5 and d examethasone, given within 4 and 8 h after the inhalation challenge, respec tively, inhibit the acute allergen-induced peak eosinophilia in BAL fluid. However, anti-IL-3, theophylline, and roxithromycin had no effect on peak e osinophilic airway inflammation after challenge. Conclusion: These observat ions suggest that several hours are needed to complete the process of cytok ine-induced recruitment of eosinophils from the blood to the airways after acute allergen challenge. This may be the optimal time to administer anti-c ytokines and dexamethasone to attenuate the subsequent eosinophilic airway inflammation after acute allergen-induced asthmatic attacks.