title: Lymphocytic bronchiolitis is associated with inadequate suppression of blood T-cell granzyme B, IFN-gamma, and TNF-alpha.
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.
authors.affiliation: Department of Thoracic Medicine, Royal Adelaide Hospital, Adelaide, South Australia, Australia. greg.hodge@health.sa.gov.au
authors.forename: Greg
authors.initials: G
authors.lastname: Hodge
authors.forename: Sandra
authors.initials: S
authors.lastname: Hodge
authors.forename: Chien
authors.initials: C
authors.lastname: Li-Liew
authors.forename: Daniel
authors.initials: D
authors.lastname: Chambers
authors.forename: Peter
authors.initials: P
authors.lastname: Hopkins
authors.forename: Paul N
authors.initials: PN
authors.lastname: Reynolds
authors.forename: Mark
authors.initials: M
authors.lastname: Holmes
mesh_terms: D001988:Bronchiolitis / Q000209:etiology* / Q000276:immunology; D018893:Bronchoalveolar Lavage; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016572:Cyclosporine / Q000097:blood / Q000627:therapeutic use; D016207:Cytokines / Q000097:blood; D053804:Granzymes / Q000037:antagonists & inhibitors* / Q000097:blood; D006801:Humans; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000097:blood / Q000627:therapeutic use; D007958:Leukocyte Count; D016040:Lung Transplantation / Q000276:immunology* / Q000401:mortality; D011183:Postoperative Complications / Q000453:epidemiology* / Q000276:immunology*; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D016559:Tacrolimus / Q000097:blood / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D016207:Cytokines; D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha; D016572:Cyclosporine; D053804:Granzymes; D016559:Tacrolimus