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Loss of glucocorticoid receptor from pro-inflammatory T cells after lung transplant.
Journal of Heart and Lung Transplantation 2014 September
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.
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.
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