Expression of corticosteroid-regulated genes by PBMCs in children with asthma.
- Resource Type
- Academic Journal
- Authors
- Goleva E; Department of Pediatrics, National Jewish Health, Denver, Colo. Electronic address: golevae@njhealth.org.; Babineau DC; Rho Federal Systems Division, Chapel Hill, NC.; Gill MA; Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Tex.; Jackson LP; Department of Pediatrics, National Jewish Health, Denver, Colo.; Shao B; Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Tex.; Hu Z; Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Tex.; Liu AH; Department of Pediatrics, National Jewish Health, Denver, Colo.; Visness CM; Rho Federal Systems Division, Chapel Hill, NC.; Sorkness CA; Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wis.; Leung DYM; Department of Pediatrics, National Jewish Health, Denver, Colo.; Togias A; National Institute of Allergy and Infectious Diseases, Bethesda, Md.; Busse WW; Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wis.
- Source
- Publisher: Mosby Country of Publication: United States NLM ID: 1275002 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1097-6825 (Electronic) Linking ISSN: 00916749 NLM ISO Abbreviation: J Allergy Clin Immunol Subsets: MEDLINE
- Subject
- Language
- English
Background: Variability in response to inhaled corticosteroids (ICSs) can result in less than optimal asthma control. Development of biomarkers assessing the therapeutic efficacy of corticosteroids is important.
Objective: We sought to examine whether in vitro PBMC responses to corticosteroids relate to the clinical ICS response.
Methods: PBMCs were collected from 125 children with asthma (6-17 years) at enrollment (visit 0 [V0]) and after 1 year of bimonthly guidelines-based management visits (visit 6 [V6]). Difficult-to-control and easy-to-control asthma were defined as requiring daily therapy with 500 μg or more of fluticasone propionate (FLU) with or without a long-acting β-agonist versus 100 μg or less of FLU in at least 4 visits. mRNA levels of glucocorticoid receptor α and corticosteroid transactivation (FK506-binding protein 5) and transrepression markers (IL-8 and TNF-α) were measured by using RT-PCR in freshly isolated cells and in response to 10 -8 mol/L FLU.
Results: Compared with PBMCs from patients with easy-to-control asthma, PBMCs from those with difficult-to-control asthma had significantly lower glucocorticoid receptor α levels at V0 (P = .05). A 30% increase in IL-8 suppression by FLU (P = .04) and a trend for increased TNF-α suppression by FLU between V0 and V6 (P = .07) were observed in patients with easy-to-control asthma. In contrast, no changes between V0 and V6 in IL-8 and TNF-α suppression by FLU were observed in patients with difficult-to-control asthma. Corticosteroid-mediated transactivation (FK506-binding protein 5 induction by FLU) increased in the PBMCs of patients with difficult-to-control and easy-to-control asthma between V0 and V6 (P = .05 and P = .03, respectively).
Conclusions: PBMCs of children with difficult-to-control asthma treated with guidelines-based therapy and requiring high-dose ICSs had reduced in vitro responsiveness to corticosteroids.
(Copyright © 2018. Published by Elsevier Inc.)