Time post-lung transplant correlates with increasing peripheral blood T cell granzyme B and proinflammatory cytokines.
Immunosuppression therapy following lung transplant fails to prevent chronic rejection/bronchiolitis obliterans syndrome, which we have shown is associated with lack of suppression of peripheral blood T cell granzyme B, interferon (IFN)-γ and tumour necrosis factor (TNF)-α. We hypothesized that these proinflammatory mediators may increase with time post-transplant in otherwise stable patients before clinical signs of declining lung function, and patients experiencing declining lung function would show a further increase in these mediators. Intracellular cytokine profiles and granzyme B were investigated in T cells in whole blood and airways from lung transplant patients using flow cytometry. There was a significant negative correlation between forced expiratory volume in 1 s (FEV(1) ), drug dose and time post-transplant. A significant correlation between increased granzyme B, IFN-γ, interleukin (IL)-2 and TNF-α and time post-transplant was noted in peripheral blood T cells but not lung T cells from stable patients. Patients with similar drug dose but experiencing declining FEV(1) showed a further increase in peripheral blood T cell IFN-γ, IL-2 and TNF-α. Time post-lung transplant correlates with increasing peripheral blood T cell granzyme B and proinflammatory cytokines. Declining FEV(1) is associated with a further increase in these proinflammatory mediators. Drugs that reduce these inflammatory mediators effectively may reduce the incidence of chronic graft rejection.
Department of Thoracic Medicine, Royal Adelaide Hospital, Adelaide, SA, Australia. greg.hodge@health.sa.gov.au
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D001379:Azathioprine / Q000627:therapeutic use; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D016572:Cyclosporine / Q000627:therapeutic use; D016207:Cytokines / Q000097:blood* / Q000378:metabolism; D004359:Drug Therapy, Combination; D005434:Flow Cytometry; D005541:Forced Expiratory Volume; D006084:Graft Rejection / Q000097:blood / Q000378:metabolism / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects / Q000276:immunology; D053804:Granzymes / Q000097:blood* / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D018836:Inflammation Mediators / Q000097:blood / Q000378:metabolism; D007371:Interferon-gamma / Q000097:blood / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D016040:Lung Transplantation; D018655:Lymphocyte Count; D011239:Prednisolone / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D016559:Tacrolimus / Q000627:therapeutic use; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000378:metabolism
D016207:Cytokines; D007166:Immunosuppressive Agents; D018836:Inflammation Mediators; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D016572:Cyclosporine; D011239:Prednisolone; D053804:Granzymes; D001379:Azathioprine; D016559:Tacrolimus