Effects of prednisone on the cellular responses and release of cytokines and mediators after segmental allergen challenge of asthmatic subjects

Background: Systemic glucocorticoids are a major therapy for the management of allergic inflammation and asthma; however, information about their effe cts in vivo are limited . Objective: This study was performed to examine the effects of prednisone on inflammatory mediators, cytokines, and cellular responses in the model of segmental allergen challenge (SAC) of allergic asthmatic subjects. Methods: The effects of a 3-day pretreatment with oral prednisone (30 mg tw ice daily) on the physiologic and inflammatory responses to SAC were studie d in 10 allergic asthmatic subjects in a double-blind, placebo-con trolled, crossover protocol. Results: Prednisone improved baseline FEV1 by 10% and modestly inhibited th e SAC-induced fall in FEV1 at 30 minutes and at 6 to 8 hours. Five minutes after challenge, levels of histamine, PGD(2),9 alpha ,11 beta -PGF(2), and thromboxane B-2 increased in bronchoalveolar lavage fluid (median increase, 5- to 14-fold); prednisone did not inhibit these responses. Prednisone inh ibited (median decrease, 66 % -97 %) the total influx of inflammatory cells , specifically eosinophils, basophils, and some subsets of T lymphocytes (C D4, CD45RA, and CD45RO cells) assessed 19 hours after SAC, but it did not i nhibit the influx of neutrophils. Increases in soluble E-selectin, kinins, and albumin were also inhibited by the glucocorticoid (median decrease, 36 %-74 %). Prednisone treatment inhibited the appearance of mRNA, protein, or both for T(H)2 cytokines (IL-4 and IL-5), as well as for IL-2 and transfor ming growth factor alpha, but did not inhibit increases of immunoreactive G M-CSF in bronchoalveolar lavage fluid. Conclusion: These studies indicate that prednisone suppresses multiple comp onents of allergic airway inflammation, including cell recruitment, adhesio n molecule expression or release, airway permeability, and production of cy tokines potentially involved in airway immunity or remodeling.