title: Usefulness of PBMCs to predict clinical response to corticosteroids in asthmatic patients.
abstract: 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.affiliation: Division of Pediatric Allergy and Immunology, National Jewish Health, Denver, CO 80206, USA.
authors.forename: Elena
authors.initials: E
authors.lastname: Goleva
authors.forename: Leisa P
authors.initials: LP
authors.lastname: Jackson
authors.forename: Melanie
authors.initials: M
authors.lastname: Gleason
authors.forename: Donald Y M
authors.initials: DY
authors.lastname: Leung
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D000328:Adult; D001249:Asthma / Q000175:diagnosis* / Q000188:drug therapy* / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D004351:Drug Resistance; D054638:Dual Specificity Phosphatase 1 / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D011241:Prednisone / Q000008:administration & dosage* / Q000009:adverse effects; D011379:Prognosis; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism; D012129:Respiratory Function Tests; D013601:T-Lymphocytes / Q000187:drug effects / Q000473:pathology
chemical_list: D000305:Adrenal Cortex Hormones; D016209:Interleukin-8; D011965:Receptors, Glucocorticoid; C121943:glucocorticoid receptor beta; D003907:Dexamethasone; D054638:Dual Specificity Phosphatase 1; D011241:Prednisone