Abstract

BackgroundIt is generally accepted that emphysematous lungs are characterized by an increase in the numbers of neutrophils, macrophages, and CD8+ T lymphocytes, the lasts having increased cytotoxic activity. Because systemic inflammation is also a component of emphysema, we hypothesize that peripheral CD8+ T lymphocytes of emphysematous smokers who show evidence of systemic inflammation will have higher expression of cytotoxic molecules.MethodsWe assessed parameters of systemic inflammation in normal individuals (smokers or non-smokers) and in emphysematous subjects with an active smoking history by measuring serum interleukine-6, C-reactive protein, and tumor necrosis factor. Expression of perforin, granzyme B, and FasL protein by CD8+ T lymphocytes, CD4+ T lymphocytes, and natural killer cells were assessed by flow cytometry while perforin, granzyme B, and FasL mRNA expression were measured on purified systemic CD8+ T lymphocytes by real-time PCR.ResultsEmphysematous smokers had higher levels of serum interleukine-6 than normal subjects. Even with the presence of systemic inflammation in emphysematous smokers, the percentage of peripheral CD8+ T lymphocytes, CD4+ T lymphocytes, and NK cells expressing perforin and granzyme B protein was not different between the three groups.ConclusionDespite evidence of systemic inflammation, peripheral T lymphocytes of emphysematous smokers did not show higher levels of cytotoxic markers, suggesting that increase of activated T lymphocytes in the emphysematous lung may be due to either activation in the lung or specific peripheral recruitment.

Highlights

  • It is generally accepted that emphysematous lungs are characterized by an increase in the numbers of neutrophils, macrophages, and CD8+ T lymphocytes, the lasts having increased cytotoxic activity

  • Subjects Twenty-nine subjects matched for age and sex were included in the study: nine were active smokers with evidence of emphysema and airflow limitation defined according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) [1] (FEV1 < 80% predicted value, FEV1/FVC < 70% predicted value, and reversibility ≤ 12% and 200 ml after salbutamol inhalation), 10 were smokers with normal lung function, and 10 were non-smokers with normal lung function

  • According to the GOLD index for chronic obstructive pulmonary disease (COPD) [1], two emphysematous smokers were classified as GOLD stage II, five as GOLD stage III, and two as GOLD stage IV

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Summary

Introduction

It is generally accepted that emphysematous lungs are characterized by an increase in the numbers of neutrophils, macrophages, and CD8+ T lymphocytes, the lasts having increased cytotoxic activity. Emphysema is a major component of chronic obstructive pulmonary disease (COPD) which is essentially induced by cigarette smoking or exposure to other noxious gases It is characterized by an inflammation-mediated destruction of the lung parenchyma which leads to distal air space enlargement and non-fully reversible airflow obstruction [1]. Chrysofakis et al [8] were able to document that perforin expression, a cytotoxic and activation marker, and cytotoxic activity of CD8+ T lymphocytes in the sputum of COPD smokers were higher than in smokers without COPD. All these data suggest that CD8+ T lymphocytes may have an important role in the pathogenesis of emphysema. Important systemic effects such as muscle wasting and cachexia are part of the disease [9,10]

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