Usefulness of PBMCs to predict clinical response to corticosteroids in asthmatic patients

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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 FEV1 of less than 80% of predicted value were classified as SR or steroid sensitive (SS) based on change in lung FEV1 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 FEV1 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.

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