TY - JOUR
T1 - Tigecycline therapy significantly reduces the concentrations of inflammatory pulmonary cytokines and chemokines in a murine model of mycoplasma pneumoniae pneumonia
AU - Salvatore, C. M.
AU - Techasaensiri, C.
AU - Tagliabue, C.
AU - Katz, K.
AU - Leos, N.
AU - Gomez, A. M.
AU - McCracken, G. H.
AU - Hardy, R. D.
PY - 2009/4
Y1 - 2009/4
N2 - Mycoplasma pneumoniae is one of the causative agents of atypical community-acquired pneumonia. Tigecy-cllne belongs to a new class of glycylcycline antimicrobials that have activity against a wide range of micro-organisms, 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 chemoklne concentrations (tumor necrosis factor alpha [TNF-et], gamma interferon [IFN-Y], interleukin Iß [IL-lß], IL-2, IL-4, IL-5, IL-6, IL-IO, IL-12 [p40/p70], granulocyte-macrophage colony-stimulating factor, MIP-Ia, MIG, KC, MCP-I, and IP-IO). BAL M. pneu-moniae 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-lß, IL-12 (p40/p70), IFN-Y, and TNF-a; of the chemokines, MIG, MIP-Ia, and IP-IO 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.
AB - Mycoplasma pneumoniae is one of the causative agents of atypical community-acquired pneumonia. Tigecy-cllne belongs to a new class of glycylcycline antimicrobials that have activity against a wide range of micro-organisms, 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 chemoklne concentrations (tumor necrosis factor alpha [TNF-et], gamma interferon [IFN-Y], interleukin Iß [IL-lß], IL-2, IL-4, IL-5, IL-6, IL-IO, IL-12 [p40/p70], granulocyte-macrophage colony-stimulating factor, MIP-Ia, MIG, KC, MCP-I, and IP-IO). BAL M. pneu-moniae 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-lß, IL-12 (p40/p70), IFN-Y, and TNF-a; of the chemokines, MIG, MIP-Ia, and IP-IO 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.
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U2 - 10.1128/AAC.00979-08
DO - 10.1128/AAC.00979-08
M3 - Article
C2 - 19139287
AN - SCOPUS:65649118628
SN - 0066-4804
VL - 53
SP - 1546
EP - 1551
JO - Antimicrobial Agents and Chemotherapy
JF - Antimicrobial Agents and Chemotherapy
IS - 4
ER -