Tigecycline Therapy Significantly Reduces the Concentrations of Inflammatory Pulmonary Cytokines and Chemokines in a Murine Model of Mycoplasma pneumoniae Pneumonia

Abstract

ABSTRACT 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-α], gamma interferon [IFN-γ], interleukin 1β [IL-1β], IL-2, IL-4, IL-5, IL-6, IL-10, IL-12 [p40/p70], granulocyte-macrophage colony-stimulating factor, MIP-1α, 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-1β, IL-12 (p40/p70), IFN-γ, and TNF-α; of the chemokines, MIG, MIP-1α, 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.