Document Detail


Usefulness of PBMCs to predict clinical response to corticosteroids in asthmatic patients.
MedLine Citation:
PMID:  22236730     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Blood tests are needed to identify steroid-resistant (SR) asthmatic patients early so that they can be managed with alternative anti-inflammatory therapy.
OBJECTIVE: We sought to assess the usefulness of peripheral blood to predict steroid response in asthmatic patients.
METHODS: Nineteen asthmatic patients with FEV(1) of less than 80% of predicted value were classified as SR or steroid sensitive (SS) based on change in lung FEV(1) percentage after 7 days of oral prednisone. Blood was collected at baseline (visit 1) and 30 days after prednisone administration (visit 3). PBMCs were cultured for 4 hours with or without 10(-7) mol/L dexamethasone, and cellular response to dexamethasone was determined by using real-time PCR based on expression analysis of steroid-regulated genes. Suppression of PHA-induced T-cell proliferation by dexamethasone was assessed.
RESULTS: Prednisone significantly improved FEV(1) percentages in SS asthmatic patients (mean ± SE: 17.5% ± 2.4%) but not SR asthmatic patients (0.8% ± 2.0%, P < .001). Before prednisone treatment, mitogen-induced kinase phosphatase 1 (P = .01) and IL-8 mRNA (P < .05) levels were significantly higher in PBMCs from SR asthmatic patients. TNF-α (P < .05) and IL-8 fold suppression by dexamethasone (P < .05) were significantly reduced in PBMCs from SR asthmatic patients. The expression of glucocorticoid receptor (GCR) β, but not GCR-α, was significantly increased in PBMCs of SR asthmatic patients (P = .01). The dexamethasone inhibitory concentration of 50% for PBMC proliferation was significantly higher for SR asthmatic patients (P < .05). These markers no longer differed between groups in PBMCs 30 days after prednisone administration. The composite score of assays at baseline before prednisone was significantly different between SR and SS asthmatic patients (P < .001).
CONCLUSIONS: PBMCs from SR asthmatic patients have higher baseline mitogen-induced kinase phosphatase 1, IL-8, and GCR-β mRNA levels; have a lower GCR-α/GCR-β mRNA ratio; are less responsive to suppression of TNF-α and IL-8 by dexamethasone; and require more dexamethasone to suppress T-cell proliferation compared with SS asthmatic patients.
Authors:
Elena Goleva; Leisa P Jackson; Melanie Gleason; Donald Y M Leung
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-01-10
Journal Detail:
Title:  The Journal of allergy and clinical immunology     Volume:  129     ISSN:  1097-6825     ISO Abbreviation:  J. Allergy Clin. Immunol.     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-03-05     Completed Date:  2012-07-06     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  1275002     Medline TA:  J Allergy Clin Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  687-693.e1     Citation Subset:  AIM; IM    
Copyright Information:
Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
Affiliation:
Division of Pediatric Allergy and Immunology, National Jewish Health, Denver, CO 80206, USA.
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MeSH Terms
Descriptor/Qualifier:
Adrenal Cortex Hormones / therapeutic use*
Adult
Asthma / diagnosis*,  drug therapy*,  immunology
Cell Proliferation / drug effects
Cells, Cultured
Dexamethasone / pharmacology
Drug Resistance
Dual Specificity Phosphatase 1 / genetics,  metabolism
Female
Humans
Interleukin-8 / genetics,  metabolism
Leukocytes, Mononuclear / drug effects,  immunology,  metabolism*,  pathology
Male
Prednisone / administration & dosage*,  adverse effects
Prognosis
Receptors, Glucocorticoid / genetics,  metabolism
Respiratory Function Tests
T-Lymphocytes / drug effects,  pathology
Grant Support
ID/Acronym/Agency:
AI070140/AI/NIAID NIH HHS; HL37260/HL/NHLBI NIH HHS; R01 AR041256-21/AR/NIAMS NIH HHS
Chemical
Reg. No./Substance:
0/Adrenal Cortex Hormones; 0/Interleukin-8; 0/Receptors, Glucocorticoid; 0/glucocorticoid receptor beta; 50-02-2/Dexamethasone; 53-03-2/Prednisone; EC 3.1.3.48/Dual Specificity Phosphatase 1
Comments/Corrections

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