Low-dose clarithromycin therapy modulates CD4+ T-cell responses in a mouse model of chronic Pseudomonas aeruginosa lung infection

Authors


Ce Shen, Department of Respiratory Medicine, The Sixth People's Hospital affiliated to Shanghai Jiao-tong University, Shanghai 200233, China. Email: lyshence@gmail.com

ABSTRACT

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.

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