Published ahead of print on April 13, 2006, doi:10.1164/rccm.200512-1930OC
© 2006 American Thoracic Society doi: 10.1164/rccm.200512-1930OC
Relative Corticosteroid Insensitivity of Peripheral Blood Mononuclear Cells in Severe AsthmaExperimental Studies, Airways Disease Section, National Heart and Lung Institute, Imperial College London and Royal Brompton NHS Trust, London, United Kingdom Correspondence and requests for reprints should be addressed to Professor Kian Fan Chung, M.D., D.Sc., National Heart & Lung Institute, Imperial College London, Dovehouse Street, London SW3 6LY, UK. E-mail: f.chung{at}imperial.ac.uk Rationale and Objectives: Patients with severe asthma have a poor therapeutic response to corticosteroid therapy, and corticosteroid responsiveness cannot be easily measured in these patients. We hypothesized that this poor response is associated with a reduced effect of corticosteroids to inhibit cytokine release from activated peripheral blood mononuclear cells (PBMCs).
Methods: Patients with severe asthma were defined by American Thoracic Society criteria. We compared the suppression of LPS-induced cytokine release (monocyte chemotactic protein-1 [MCP-1], macrophage inflammatory protein [MIP] 1
Results: There was no difference in baseline spontaneous or stimulated release of these cytokines among groups. LPS-induced release of 10 cytokines was less suppressed by dexamethasone (10–6 M) in patients with severe asthma compared with patients with nonsevere asthma, with statistical significance achieved for IL-1 Conclusions: Patients with severe asthma have diminished corticosteroid sensitivity of PBMCs when compared with patients with nonsevere asthma, associated with a reduction in HDAC activity that parallels the impaired corticosteroid sensitivity.
Key Words: corticosteroids • histone acetyltransferase • histone deacetylase • severe asthma This article has been cited by other articles:
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, RANTES, tumor necrosis factor 
(IL-1
, IL-6, IL-10, and granulocyte-macrophage colony–stimulating factor [GM-CSF]) by dexamethasone from PBMCs of patients with severe asthma (n = 16), patients with nonsevere asthma (n = 19), and normal volunteers (n = 10). 
