IngentaConnect Increased intracellular T helper 1 proinflammatory cytokine produ...

Abstract:

Summary

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)-α 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 (FEV₁) and the percentage of BAL and intraepithelial CD8⁺ T cells producing TNF-α. 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-α production by CD8⁺ T cells may improve morbidity in COPD patients while targeting of TNF-α in the lung may prevent smokers progressing to COPD.

Keywords: COPD; intracellular Th1 proinflammatory cytokines; CD8+ T cells; flow cytometry

Document Type: Research article

DOI: 10.1111/j.1365-2249.2007.03451.x

Affiliations: 1: Department of Thoracic Medicine, Royal Adelaide Hospital, Adelaide, and

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Increased intracellular T helper 1 proinflammatory cytokine production in peripheral blood, bronchoalveolar lavage and intraepithelial T cells of COPD subjects