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

Mark C. Liu; David Proud; Lawrence M. Lichtenstein; Walter C. Hubbard; Bruce S. Bochner; Becky A. Stealey; Linda Breslin; Hui Qing Xiao; Linda R. Freidhoff; John T. Schroeder; Robert P. Schleimer

doi:10.1067/mai.2001.116004

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

Mark C. Liu, David Proud, Lawrence M. Lichtenstein, Walter C. Hubbard, Bruce S. Bochner, Becky A. Stealey, Linda Breslin, Hui Qing Xiao, Linda R. Freidhoff, John T. Schroeder, Robert P. Schleimer

Medicine, Allergy Division

Research output: Contribution to journal › Article › peer-review

73 Scopus citations

Abstract

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 T_H2 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.

Original language	English (US)
Pages (from-to)	29-38
Number of pages	10
Journal	Journal of Allergy and Clinical Immunology
Volume	108
Issue number	1
DOIs	https://doi.org/10.1067/mai.2001.116004
State	Published - 2001

Funding

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

Keywords

Asthma
Cytokines
Glucocorticoids
Inflammation

ASJC Scopus subject areas

Immunology and Allergy
Immunology

Access to Document

10.1067/mai.2001.116004

Cite this

Liu, M. C., Proud, D., Lichtenstein, L. M., Hubbard, W. C., Bochner, B. S., Stealey, B. A., Breslin, L., Xiao, H. Q., Freidhoff, L. R., Schroeder, J. T., & Schleimer, R. P. (2001). Effects of prednisone on the cellular responses and release of cytokines and mediators after segmental allergen challenge of asthmatic subjects. Journal of Allergy and Clinical Immunology, 108(1), 29-38. https://doi.org/10.1067/mai.2001.116004

@article{b291bbb86b1b4f39bf12adfc072ff0a6,

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

abstract = "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.",

keywords = "Asthma, Cytokines, Glucocorticoids, Inflammation",

author = "Liu, {Mark C.} and David Proud and Lichtenstein, {Lawrence M.} and Hubbard, {Walter C.} and Bochner, {Bruce S.} and Stealey, {Becky A.} and Linda Breslin and Xiao, {Hui Qing} and Freidhoff, {Linda R.} and Schroeder, {John T.} and Schleimer, {Robert P.}",

note = "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 {\textcopyright} 2001 by Mosby, Inc. 0091-6749/2001 $35.00 + 0 1/83/116004 doi:10.1067/mai.2001.116004",

year = "2001",

doi = "10.1067/mai.2001.116004",

language = "English (US)",

volume = "108",

pages = "29--38",

journal = "Journal of Allergy and Clinical Immunology",

issn = "0091-6749",

publisher = "Mosby Inc.",

number = "1",

}

Liu, MC, Proud, D, Lichtenstein, LM, Hubbard, WC, Bochner, BS, Stealey, BA, Breslin, L, Xiao, HQ, Freidhoff, LR, Schroeder, JT & Schleimer, RP 2001, 'Effects of prednisone on the cellular responses and release of cytokines and mediators after segmental allergen challenge of asthmatic subjects', Journal of Allergy and Clinical Immunology, vol. 108, no. 1, pp. 29-38. https://doi.org/10.1067/mai.2001.116004

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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SN - 0091-6749

VL - 108

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JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

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

Abstract

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