Relative corticosteroid insensitivity of peripheral blood mononuclear cells in severe asthma.

American Journal of Respiratory and Critical Care Medicine
Mark HewKian Fan Chung

Abstract

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). 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] 1alpha, RANTES, tumor necrosis factor alpha, interleukin 1beta (IL-1beta), IL-8, IFN-gamma, 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). 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-1beta (p < 0.03), IL-8 (p < 0.03), and MIP-1alpha (p < 0.00...Continue Reading

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Jun 27, 2009·European Journal of Clinical Pharmacology·Kian Fan ChungIan M Adcock
Apr 18, 2008·Current Allergy and Asthma Reports·Ian M AdcockKian Fan Chung
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