1. Lymphocytic bronchiolitis is associated with inadequate suppression of blood T-cell granzyme B, IFN-gamma, and TNF-alpha.
- Author
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Hodge G, Hodge S, Li-Liew C, Chambers D, Hopkins P, Reynolds PN, and Holmes M
- Subjects
- Bronchiolitis immunology, Bronchoalveolar Lavage, CD4-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes immunology, Cyclosporine blood, Cyclosporine therapeutic use, Cytokines blood, Granzymes blood, Humans, Immunosuppression Therapy, Immunosuppressive Agents blood, Immunosuppressive Agents therapeutic use, Leukocyte Count, Lung Transplantation mortality, Survival Analysis, T-Lymphocytes enzymology, T-Lymphocytes, Regulatory immunology, Tacrolimus blood, Tacrolimus therapeutic use, Bronchiolitis etiology, Granzymes antagonists & inhibitors, Lung Transplantation immunology, Postoperative Complications epidemiology, Postoperative Complications immunology, T-Lymphocytes immunology, Tumor Necrosis Factor-alpha antagonists & inhibitors
- Abstract
Background: Lymphocytic bronchiolitis (LB) has been shown to be an important factor for the subsequent development of obliterative bronchiolitis (OB). We have previously shown that OB, which limits long-term survival after lung transplantation, is associated with lack of suppression of peripheral blood T-cell granzyme B, interferon (IFN)-gamma, and tumor necrosis factor (TNF)-alpha. However, the role of these proinflammatory mediators in LB is unknown. We hypothesized that these proinflammatory mediators may also be increased during LB episodes despite standard immunosuppression regimens., Methods: T-cell intracellular cytokine profiles and granzyme B were studied in whole blood, bronchoalveolar lavage samples, and bronchial brushings from stable lung transplant patients with LB and from healthy controls, using multiparameter flow cytometry., Results: There was a significant increase in peripheral blood T-cell granzyme B and CD8 T-cell IFN-gamma and TNF-alpha in patients with LB compared with control and stable groups and a decrease in CD25CD127CD3CD8 T regulatory cells in stable and LB transplant patients compared with controls. No changes were noted in the airways., Conclusions: LB is associated with inadequate suppression of peripheral blood T-cell granzyme B, IFN-gamma, and TNF-alpha. Drugs that effectively reduce these proinflammatory mediators may improve current protocols for treating LB and possibly reduce subsequent progression to OB in lung transplant patients.
- Published
- 2010
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