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Low‐dose clarithromycin therapy modulates CD4 + T‐cell responses in a mouse model of chronic Pseudomonas aeruginosa lung infection
Author(s) -
DING FENGMING,
ZHU SONGLEI,
SHEN CE,
JIANG YANQUN
Publication year - 2012
Publication title -
respirology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 85
eISSN - 1440-1843
pISSN - 1323-7799
DOI - 10.1111/j.1440-1843.2012.02166.x
Subject(s) - bronchoalveolar lavage , medicine , saline , immune system , immunology , t cell , clarithromycin , t helper cell , cell , interleukin , cytokine , cd8 , lung , biology , genetics , helicobacter pylori
Background and objective: Low‐dose clarithromycin (CAM) is widely used for the treatment of chronic respiratory infections. However, its anti‐inflammatory mechanisms have not been fully explored. As CD4 + T cells play an important role in the initiation of immune responses to infectious microorganisms, we aimed to investigate the effects of low‐dose CAM on CD4 + T‐cell responses. Methods: Fifty‐four BALB/c mice were randomly divided into three groups: a control group (inoculated with sterile agarose beads and treated with saline from day 7), a saline group (inoculated with Pseudomonas aeruginosa ‐loaded beads and treated with saline from day 7) and a CAM group (identical to the saline group, except that saline was replaced by CAM solution). Bronchoalveolar lavage (BAL) fluid cell counts, bacterial load, lung tissue histology and pulmonary CD3 + CD4 + cell numbers were assessed. Levels of T helper (Th)1/Th2/Th17 cytokines and suppressor cytokines (interleukin (IL)‐10 and transforming growth factor‐β1) were analysed. Messenger RNA (mRNA) levels for transcription factors for CD4 + T‐cell subsets were determined. Results: The CAM group had lower BAL fluid cell counts, pathological scores and pulmonary CD3 + CD4 + cell numbers compared with the saline group, whereas the bacterial load was not significantly different. Levels of Th1/Th17 cytokines and expression of a transcription factor for naturally occurring regulatory T cells (Treg) were significantly decreased in the CAM group compared with the saline group, whereas there was no significant difference in GATA‐3 mRNA expression. Conclusions: This study demonstrated a downregulation of Th1/Th17/naturally occurring Treg responses after treatment with low‐dose CAM in mice with chronic P. aeruginosa lung infection.