Increased intracellular pro- and anti-inflammatory cytokines in bronchoalveolar lavage T cells of stable lung transplant patients.
BACKGROUND
Allograft rejection remains a major cause of morbidity and mortality following lung transplantation and is associated with an increased expression of T-cell proinflammatory cytokines. We have recently shown that peripheral blood T-cell proinflammatory cytokine production was significantly reduced in stable lung transplant patients consistent with immunosuppression therapy. However, analysis of inflammatory cytokine profiles in bronchoalveolar lavage (BAL) T cells may be more relevant than peripheral blood T cells for assessing graft status.


METHODS
To investigate the immunomodulatory effects of currently used immunosuppressive regimens on BAL T-cell cytokine production, whole blood and BAL from stable lung transplant patients and control volunteers was stimulated in vitro and cytokine production by CD8+ and CD4+ T-cell subsets determined using multiparameter flow cytometry.


RESULTS
There was a significant decrease in T-cell proinflammatory cytokine production in BAL compared with blood from control subjects but not transplant patients. Anti-inflammatory cytokine IL-4 was increased in BAL compared with blood from both groups. There was a significant increase in IFNgamma, IL-2, IL-4, TGFbeta, and TNFalpha production by CD8 T cells and IFNgamma and TNFalpha production by CD4 T cells in BAL from transplant patients compared with controls.


CONCLUSIONS
We have shown decreased T-cell pro- and anti-inflammatory cytokine production in BAL compared with blood in control subjects but not in stable lung transplant patients. Current immunosuppression protocols have limited effect on T-cell proinflammatory cytokine production in BAL but do upregulate anti-inflammatory cytokines IL-4 and TGFbeta. Drugs that effectively reduce T-cell proinflammatory cytokine production in BAL may improve current protocols for reducing graft rejection in these patients.
Hodge
Greg
G
Department of Thoracic Medicine, Royal Adelaide Hospital, Adelaide, Australia. hodgeg@mail.wch.sa.gov.au
Hodge
Sandra
S
Reynolds
Paul N
PN
Holmes
Mark
M
D000328:Adult; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology*; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000187:drug effects / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry / Q000187:drug effects / Q000276:immunology*; D016207:Cytokines / Q000032:analysis / Q000378:metabolism*; D005260:Female; D006084:Graft Rejection / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008168:Lung / Q000276:immunology; D016040:Lung Transplantation / Q000276:immunology*; D008297:Male
D016207:Cytokines; D007166:Immunosuppressive Agents