Tigecycline therapy significantly reduces the concentrations of inflammatory pulmonary cytokines and chemokines in a murine model of Mycoplasma pneumoniae pneumonia.
Mycoplasma pneumoniae is one of the causative agents of atypical community-acquired pneumonia. Tigecycline belongs to a new class of glycylcycline antimicrobials that have activity against a wide range of microorganisms, including in vitro activity against M. pneumoniae. We investigated the effect of tigecycline on microbiologic, histologic, and immunologic indices in a murine model of M. pneumoniae pneumonia. BALB/c mice were inoculated intranasally with M. pneumoniae and treated subcutaneously with tigecycline or placebo for 6 days. Outcome variables included quantitative bronchoalveolar lavage (BAL) M. pneumoniae culture, lung histopathologic score (HPS), BAL cytokine and chemokine concentrations (tumor necrosis factor alpha [TNF-alpha], gamma interferon [IFN-gamma], interleukin 1beta [IL-1beta], IL-2, IL-4, IL-5, IL-6, IL-10, IL-12 [p40/p70], granulocyte-macrophage colony-stimulating factor, MIP-1alpha, MIG, KC, MCP-1, and IP-10). BAL M. pneumoniae concentrations in mice treated with tigecycline (MpTige) tended to be reduced compared with mice treated with placebo (MpPl); however this did not reach statistical significance. The lung HPS was significantly lower, as well as the parenchymal-pneumonia subscore, in the MpTige mice than in the MpPl mice. MpTige mice had significantly lower BAL cytokine concentrations of IL-1beta, IL-12 (p40/p70), IFN-gamma, and TNF-alpha; of the chemokines, MIG, MIP-1alpha, and IP-10 were statistically lower in MpTige mice. While tigecycline treatment demonstrated a modest microbiologic effect, it significantly improved lung histologic inflammation and reduced pulmonary cytokines and chemokines.
Salvatore
C M
CM
Departments of Pediatric Infectious Diseases, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9063, USA.
Techasaensiri
C
C
Tagliabue
C
C
Katz
K
K
Leos
N
N
Gomez
A M
AM
McCracken
G H
GH
Hardy
R D
RD
D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D018925:Chemokines / Q000032:analysis*; D016207:Cytokines / Q000032:analysis*; D004195:Disease Models, Animal; D005260:Female; D008168:Lung / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008911:Minocycline / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D011019:Pneumonia, Mycoplasma / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D000078304:Tigecycline
D000900:Anti-Bacterial Agents; D018925:Chemokines; D016207:Cytokines; D000078304:Tigecycline; D008911:Minocycline