TY - JOUR
T1 - Effects of prednisone on the cellular responses and release of cytokines and mediators after segmental allergen challenge of asthmatic subjects
AU - Liu, Mark C.
AU - Proud, David
AU - Lichtenstein, Lawrence M.
AU - Hubbard, Walter C.
AU - Bochner, Bruce S.
AU - Stealey, Becky A.
AU - Breslin, Linda
AU - Xiao, Hui Qing
AU - Freidhoff, Linda R.
AU - Schroeder, John T.
AU - Schleimer, Robert P.
N1 - Funding Information:
From Johns Hopkins University School of Medicine at the Johns Hopkins Asthma and Allergy Center, Baltimore. Supported by National Institute of Health grants P01 HL 49545, U19 AI31867, R01 AI31891, and AI44885. Received for publication September 18, 2000; revised March 14, 2001; accepted for publication March 16, 2001. Reprint requests: Mark C. Liu, MD, Johns Hopkins Asthma and Allergy Cen-ter, 5501 Hopkins Bayview Circle, Baltimore, MD 21224-6801. Copyright © 2001 by Mosby, Inc. 0091-6749/2001 $35.00 + 0 1/83/116004 doi:10.1067/mai.2001.116004
PY - 2001
Y1 - 2001
N2 - Background: Systemic glucocorticoids are a major therapy for the management of allergic inflammation and asthma; however, information about their effects 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 twice daily) on the physiologic and inflammatory responses to SAC were studied in 10 allergic asthmatic subjects in a double-blind, placebo-controlled, crossover protocol. Results: Prednisone improved baseline FEV1 by 10% and modestly inhibited the SAC-induced fall in FEV1 at 30 minutes and at 6 to 8 hours. Five minutes after challenge, levels of histamine, PGD2, 9α, 11β-PGF2, and thromboxane B2 increased in bronchoalveolar lavage fluid (median increase, 5- to 14-fold); prednisone did not inhibit these responses. Prednisone inhibited (median decrease, 66%-97%) the total influx of inflammatory cells, specifically eosinophils, basophils, and some subsets of T lymphocytes (CD4, CD45RA, and CD45RO cells) assessed 19 hours after SAC, but it did not inhibit 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 TH2 cytokines (IL-4 and IL-5), as well as for IL-2 and transforming growth factor α, but did not inhibit increases of immunoreactive GM-CSF in bronchoalveolar lavage fluid. Conclusion: These studies indicate that prednisone suppresses multiple components of allergic airway inflammation, including cell recruitment, adhesion molecule expression or release, airway permeability, and production of cytokines potentially involved in airway immunity or remodeling.
AB - Background: Systemic glucocorticoids are a major therapy for the management of allergic inflammation and asthma; however, information about their effects 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 twice daily) on the physiologic and inflammatory responses to SAC were studied in 10 allergic asthmatic subjects in a double-blind, placebo-controlled, crossover protocol. Results: Prednisone improved baseline FEV1 by 10% and modestly inhibited the SAC-induced fall in FEV1 at 30 minutes and at 6 to 8 hours. Five minutes after challenge, levels of histamine, PGD2, 9α, 11β-PGF2, and thromboxane B2 increased in bronchoalveolar lavage fluid (median increase, 5- to 14-fold); prednisone did not inhibit these responses. Prednisone inhibited (median decrease, 66%-97%) the total influx of inflammatory cells, specifically eosinophils, basophils, and some subsets of T lymphocytes (CD4, CD45RA, and CD45RO cells) assessed 19 hours after SAC, but it did not inhibit 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 TH2 cytokines (IL-4 and IL-5), as well as for IL-2 and transforming growth factor α, but did not inhibit increases of immunoreactive GM-CSF in bronchoalveolar lavage fluid. Conclusion: These studies indicate that prednisone suppresses multiple components of allergic airway inflammation, including cell recruitment, adhesion molecule expression or release, airway permeability, and production of cytokines potentially involved in airway immunity or remodeling.
KW - Asthma
KW - Cytokines
KW - Glucocorticoids
KW - Inflammation
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U2 - 10.1067/mai.2001.116004
DO - 10.1067/mai.2001.116004
M3 - Article
C2 - 11447379
AN - SCOPUS:0034919083
SN - 0091-6749
VL - 108
SP - 29
EP - 38
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
IS - 1
ER -