Antimicrobial and Immunologic Activities of Clarithromycin in a Murine Model of Mycoplasma pneumoniae -Induced Pneumonia

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Abstract
Because macrolide antibiotics are hypothesized to possess immunomodulatory activity independent of their antimicrobial activity, we evaluated the immunomodulatory effect of clarithromycin in a murine model of lung inflammation induced by either live or UV-killed Mycoplasma pneumoniae . BALB/c mice were intranasally inoculated once with live or UV-killed M . pneumoniae . Clarithromycin (25 mg/kg of body weight) or placebo was subcutaneously administered once daily in both groups of mice. In mice infected with live M . pneumoniae , clarithromycin treatment significantly reduced quantitative M . pneumoniae bronchoalveolar lavage (BAL) culture, pulmonary histopathologic scores (HPS), and airway resistance-obstruction (as measured by plethysmography) compared with placebo. Concentrations of tumor necrosis factor alpha, gamma interferon, interleukin-6 (IL-6), mouse KC (functional IL-8), JE/MCP-1, and MIP-1α in BAL fluid were also significantly decreased in mice infected with live M . pneumoniae given clarithromycin. In contrast, mice inoculated with UV-killed M . pneumoniae had no significant reduction in HPS, airway resistance-obstruction, or BAL cytokine or chemokine concentrations in response to clarithromycin administration. Clarithromycin therapy demonstrated beneficial effects (microbiologic, histologic, respiratory, and immunologic) on pneumonia in the mice infected with live M . pneumoniae ; this was not observed in the mice inoculated with UV-killed M . pneumoniae .