Increased intracellular T helper 1 proinflammatory cytokine production in peripheral blood, bronchoalveolar lavage and intraepithelial T cells of COPD subjects.
The role of T cells in the pathophysiology of chronic obstructive pulmonary disease (COPD) is not yet certain, although varying reports have shown increases in T helper 1 (Th1) and/or Th2 cytokines in peripheral blood and bronchoalveolar lavage (BAL). No studies have examined cytokine production by intraepithelial T cells obtained by bronchial brushing (BB). Intracellular cytokine analysis of T cell subsets from peripheral blood, BAL and BB from smoker and ex-smoker COPD patients, COPD patients receiving inhaled corticosteroids and smoker and non-smoker control subjects was studied using multi-parameter flow cytometry. CD4 : CD8 inversion was noted in the peripheral blood of smoker and ex-smoker COPD groups, in BAL and BB from smoker controls and BAL of COPD smokers. There was an increase in intracellular CD8(+) T cell Th1 proinflammatory cytokines in some COPD groups in the peripheral blood and in CD8(+) T cell tumour necrosis factor (TNF)-alpha in some COPD groups and smoker controls in BAL and BB. There was an increase in proinflammatory cytokines in COPD smokers compared with ex-smokers and a decrease in COPD smokers receiving inhaled corticosteroids in the airways. There was a negative correlation between forced expiratory volume in 1 s (FEV(1)) and the percentage of BAL and intraepithelial CD8(+) T cells producing TNF-alpha. COPD patients exhibit systemic inflammation as evidenced by increased intracellular Th1 proinflammatory cytokines in blood, BAL and intraepithelial CD8(+) T cells, whereas smoker controls showed localized Th1 response in the lung only. Systemic therapeutic targeting of TNF-alpha production by CD8(+) T cells may improve morbidity in COPD patients while targeting of TNF-alpha in the lung may prevent smokers progressing to COPD.
Hodge
G
G
Department of Thoracic Medicine, Royal Adelaide Hospital, Australia. greg.hodge@cywhs.sa.gov.au
Nairn
J
J
Holmes
M
M
Reynolds
P N
PN
Hodge
S
S
D000328:Adult; D000368:Aged; D001980:Bronchi / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology*; D001999:Bronchoscopy; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D005541:Forced Expiratory Volume / Q000276:immunology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology*; D020545:Respiratory Mucosa / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*
D016207:Cytokines; D018836:Inflammation Mediators