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.
Hodge
G
G
Department of Thoracic Medicine, Royal Adelaide Hospital, Adelaide, SA, Australia. greg.hodge@health.sa.gov.au
Hodge
S
S
Li-Liew
C
C
Chambers
D
D
Hopkins
P
P
Reynolds
P N
PN
Holmes
M
M
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