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Antimicrobial Agents and Chemotherapy, May 2003, p. 1614-1620, Vol. 47, No. 5
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.5.1614-1620.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

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

Robert D. Hardy,1,2* Ana Maria Rios,1 Susana Chavez-Bueno,1 Hasan S. Jafri,1 Jeanine Hatfield,1 Beverly B. Rogers,3 George H. McCracken,1 and Octavio Ramilo1

Departments of Pediatrics,1 Internal Medicine (Division of Infectious Diseases),2 Pathology, University of Texas Southwestern Medical Center, Dallas, Texas3

Received 13 August 2002/ Returned for modification 25 November 2002/ Accepted 3 February 2003

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-1{alpha} 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.

* Corresponding author. Mailing address: Department of Pediatrics, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9063. Phone: (214) 648-3720. Fax: (214) 648-2961. E-mail: robert.hardy{at}utsouthwestern.edu.

Antimicrobial Agents and Chemotherapy, May 2003, p. 1614-1620, Vol. 47, No. 5
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.5.1614-1620.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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