title: Low-dose clarithromycin therapy modulates CD4(+)  T-cell responses in a mouse model of chronic Pseudomonas aeruginosa lung infection.
abstract: 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.
authors.affiliation: Department of Respiratory Medicine, The Sixth People's Hospital affiliated to Shanghai Jiao-tong University, Shanghai, China.
authors.forename: Feng-Ming
authors.initials: FM
authors.lastname: Ding
authors.forename: Song-Lei
authors.initials: SL
authors.lastname: Zhu
authors.forename: Ce
authors.initials: C
authors.lastname: Shen
authors.forename: Yan-Qun
authors.initials: YQ
authors.lastname: Jiang
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D018893:Bronchoalveolar Lavage; D017291:Clarithromycin / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D007150:Immunohistochemistry; D020381:Interleukin-17 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008171:Lung Diseases / Q000276:immunology / Q000382:microbiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000276:immunology*; D011550:Pseudomonas aeruginosa; D060888:Real-Time Polymerase Chain Reaction; D012141:Respiratory Tract Infections / Q000188:drug therapy / Q000276:immunology* / Q000382:microbiology; D013234:Stem Cells; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D020381:Interleukin-17; D015847:Interleukin-4; D017291:Clarithromycin