Background: Chronic obstructive pulmonary disease (COPD) is characterized by airway inflammation and is associated with acute exacerbations. Macrolide antibiotics have been shown to exhibit anti-inflammatory effects in some chronic airway inflammatory diseases. Objective: The aim of this study was to assess the effect of treatment with erythromycin on airway inflammation and health outcome in COPD patients. Methods: We conducted a randomized, placebo-controlled, double-blind trial of erythromycin for a period of 6 months. Thirty-six COPD patients were randomized to treatment with oral erythromycin (125 mg, three times/day) or placebo. The primary outcomes were neutrophil number in sputum and exacerbations. Results: Thirty-one patients completed the study. At the end of treatment, neutrophil counts in the sputum were significantly decreased in the group treated with erythromycin compared with placebo-treated patients (p = 0.005). Total cells in the sputum and neutrophil elastase in sputum supernatant were also significantly decreased in those treated with erythromycin compared with the placebo group (p = 0.021 and p = 0.024, respectively). The mean exacerbation rate was lower in the erythromycin group than in the placebo group (relative risk = 0.554, p = 0.042). Kaplan-Meier survival analysis showed that erythromycin significantly delayed the time to the first COPD exacerbation compared with placebo (p = 0.032). Conclusions: Erythromycin treatment in COPD patients can reduce airway inflammation and decrease exacerbations and may therefore be useful in the management of COPD.

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Purpose: The aim of this study was to explore the presence of the chemokines CCL22 and CCL17 in malignant pleural effusion, and the chemoattractant activity of these chemokines on CD4-positive CD25-positive Foxp3-positive regulatory Tcells infiltrating into the pleural space. Experimental Design: The concentrations of CCL22 and CCL17 in both pleural effusions and sera from 33 patients with lung cancer were determined. Flow cytometry was done to determine T lymphocyte subsets in cell pellets of pleural effusion. Pleural cells were analyzed for the expression of CCL22 and CCL17. The chemoattractant activity of CCL22 for regulatory T cells in vitro and in vivo was also observed. Results: The concentration of CCL22 in malignant pleural effusion was significantly higher than that in the corresponding serum. Pleural fluid from lung cancer patients was chemotactic for regulatory T cells, and this activity was partly blocked by an anti-CCL22, but not by an anti-CCL17 antibody. Intrapleural administration of CCL22 of patients produced a marked progressive influx of regulatory T cells into pleural space. Conclusions: Compared with serum, CCL22 seemed to be increased in malignant pleural effusion, and could directly induce regulatory T cell infiltration into the pleural space in patients with malignant effusion.The development of inflammatory processes in the pleural space may result in increased pleural vascular permeability leading to the accumulation of fluid enriched in proteins, and the recruitment of cells into the pleural space (1). Although malignant pleural effusion is more and more common, very little information is available on the immune mechanisms that are involved in its development. An accumulation of lymphocytes, especially CD4-positive T lymphocytes, frequently occurs in malignant pleural effusion secondary to direct pleural involvement and/or metastases from malignancies (2, 3).Studies ongoing for more than a decade have provided firm evidence for the existence of a unique CD4-positive CD25-positive T-cell population of ''professional'' regulatory/suppressor T cells that actively and dominantly prevent both the activation and the effector function of autoreactive T cells that have escaped other mechanisms of tolerance (4 -6). CD4-positive CD25-positive Foxp3-positive regulatory T cells are believed to be involved in the control of the local immune response and in the growth of human lung cancer (7 -9). Our previous studies have shown that regulatory T cells infiltrating into human malignant pleural effusion behave as regulatory T cells (10). However, the mechanism by which regulatory T cells infiltrate into malignant pleural effusion is unknown so far. It has been reported that the chemokines CCL22 and CCL17 within the microenvironment of gastric cancer were related to the high frequency of regulatory T cells in tumorinfiltrating lymphocytes, with such an observation occurring in the early stage of gastric cancer (11). In addition, patients with malignant pleural effusion have higher percentages ...