Antimicrobial and immunologic activities of clarithromycin in a murine model of Mycoplasma pneumoniae-induced pneumonia.
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-1alpha 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.
Hardy
Robert D
RD
Departments of Pediatrics. Internal Medicine, Division of Infectious Diseases, University of Texas Southwestern Medical Center, Dallas, USA. robert.hardy@utsouthwestern.edu
Rios
Ana Maria
AM
Chavez-Bueno
Susana
S
Jafri
Hasan S
HS
Hatfield
Jeanine
J
Rogers
Beverly B
BB
McCracken
George H
GH
Ramilo
Octavio
O
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology / Q000382:microbiology; D018925:Chemokines / Q000032:analysis; D017291:Clarithromycin / Q000494:pharmacology / Q000627:therapeutic use*; D016207:Cytokines / Q000032:analysis; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D010991:Plethysmography; D011019:Pneumonia, Mycoplasma / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology
D018925:Chemokines; D016207:Cytokines; D017291:Clarithromycin