Impact of azithromycin on the migration of peripheral blood T lymphocytes from patients with chronic obstructive pulmonary disease to RANTES and IP-10

Abstract

The inflammatory process specific for chronic obstructive pulmonary disease (COPD) is accompanied by T lymphocyte migration from peripheral blood to the respiratory tract. Suppression of T cell chemotaxis by drugs may attenuate the inflammatory response in patients with COPD.The aim of this study was to determine the ability of azithromycin in combination with glucocorticoids to affect the migration of blood T cells in patients with COPD.The percentage of T lymphocytes expressing chemokine receptors CCR5, CCR6, CCR7, CXCR3, CXCR4, CXCR6 was analyzed by flow cytometry in the peripheral blood of 54 smokers with COPD, 21 healthy smokers, and 20 healthy non-smokers, as well as in bronchoalveolar lavage (BAL) of 7 smokers with COPD and 7 healthy smokers. Additionally, we determined the effect of azithromycin (10 μg/ml) and budesonide (10 nM) on the migration of peripheral blood T helper cells and cytotoxic T lymphocytes from patients with COPD (n = 8) to chemokines RANTES (10 nM) and IP-10 (10 nM).The percentage of T lymphocytes expressing chemokine receptors CXCR3 and CCR5 increased in the peripheral blood of COPD smokers compared with healthy smokers and healthy non-smokers, as well as in the BAL of COPD smokers compared with healthy smokers. The proportion of T cells expressing chemokine receptors CXCR4, CXCR6, CCR6, and CCR7 did not differ in the peripheral blood and the BAL between COPD patients and healthy controls. Budesonide only inhibited the migration of cytotoxic T lymphocytes to RANTES. Azithromycin, alone and combined with budesonide, inhibited the migration of T helper cells and cytotoxic T lymphocytes to both RANTES and IP-10. Moreover, the inhibitory effect of azithromycin, in combination with budesonide and without it, on the T cell migration was significantly greater than the effect of budesonide alone.Our results suggest a role for CXCR3 and CCR5 in T cell recruitment into the lungs of COPD patients and demonstrate the ability of azithromycin to inhibit T lymphocyte migration.