title: Loss of glucocorticoid receptor from pro-inflammatory T cells after lung transplant.
abstract: BACKGROUND
  Pro-inflammatory cytokines in T and natural killer T (NKT)-like cells increase with time post-transplant in otherwise stable patients, suggesting that some patients become relatively resistant to immunosuppressants such as glucocorticoids (GC). We hypothesized that GC receptor (GCR) would be down-regulated in peripheral blood pro-inflammatory T and NKT-like cells after lung transplantation and loss of GCR would correlate with time post-transplant.
  
  
  METHODS
  Blood was collected from 17 stable lung transplant patients and 17 healthy, aged-matched controls. Intracellular GCR expression and pro-inflammatory cytokines were determined using flow cytometry.
  
  
  RESULTS
  There was a loss of GCR in CD8(+) and CD8(-) T and NKT-like cells in transplant patients compared with control subjects (transplants 37 ± 9%, controls 47 ± 12%; GCR(+)CD8(+) and CD8(-) T cells: transplants 39 ± 13%, controls 58 ± 13%). Loss of GCR was associated with a greater percentage of T cells producing interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) but not NKT-like cells. There was a correlation between the percentage of GCR-negative T cells with months post-transplant (R = 0.519, p = 0.033) and dose of prednisolone (R = 0.775, p = 0.038).
  
  
  CONCLUSIONS
  Time post-transplant and prednisolone dose correlate with loss of GCR in pro-inflammatory T cells in stable transplant patients, suggesting the need for reassessment of the long-term use of steroids after lung transplant in view of their attendant significant side effects.
authors.affiliation: Lung Research, Hanson Institute, and Department of Thoracic Medicine, Royal Adelaide Hospital; Department of Medicine, University of Adelaide. Electronic address: greg.hodge@health.sa.gov.au.
authors.forename: Greg
authors.initials: G
authors.lastname: Hodge
authors.affiliation: Lung Research, Hanson Institute, and Department of Thoracic Medicine, Royal Adelaide Hospital; Department of Medicine, University of Adelaide.
authors.forename: Sandra
authors.initials: S
authors.lastname: Hodge
authors.affiliation: Lung Research, Hanson Institute, and Department of Thoracic Medicine, Royal Adelaide Hospital; Department of Medicine, University of Adelaide; South Australian Lung Transplant Service, Adelaide, South Australia, Australia.
authors.forename: Chien Li
authors.initials: CL
authors.lastname: Holmes-Liew
authors.affiliation: Lung Research, Hanson Institute, and Department of Thoracic Medicine, Royal Adelaide Hospital; Department of Medicine, University of Adelaide.
authors.forename: Paul N
authors.initials: PN
authors.lastname: Reynolds
authors.affiliation: Lung Research, Hanson Institute, and Department of Thoracic Medicine, Royal Adelaide Hospital; Department of Medicine, University of Adelaide; South Australian Lung Transplant Service, Adelaide, South Australia, Australia.
authors.forename: Mark
authors.initials: M
authors.lastname: Holmes
mesh_terms: D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D007371:Interferon-gamma / Q000378:metabolism; D008171:Lung Diseases / Q000601:surgery*; D016040:Lung Transplantation; D008875:Middle Aged; D055611:Natural Killer T-Cells / Q000378:metabolism* / Q000473:pathology; D011184:Postoperative Period; D011239:Prednisolone / Q000627:therapeutic use; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D011239:Prednisolone
keywords: GCR; IFN-γ; T cells; TNF-α; lung transplant