he host. In addition, it has recently been reported that Nox2, which is expressed at high levels in inflammatory cells, including neutrophils, and serves as 
a major source of ROS in infectious diseases, is produced at excessively high levels during influenza infections, leading to a deterioration in the overall health of the patient, and is considered to be a key molecule in the development of influenza virus-induced pneumonia. Therefore, it has been proposed that scavengers of ROS or RNOS could represent a potentially new therapeutic strategy for the treatment of influenza virus-induced pneumonia. In fact, a number of compounds, including N-acetyl-cysteine, superoxide dismutase, catalase, thioredoxin, NG-Monomethyl-L-arginine that possess scavenger or inhibitor activity against free radicals, but do not show an antivirus effect, have been reported to be effective in treating mice that had been infected with the influenza virus. Since the pulmonary damage induced by an influenza virus infection increases the risk of a secondary infection by bacteria, such as a pneumococcus, an anti-oxidant therapy is also important from the point of view of suppressing secondary bacterial infections. Fluoroquinolones, antimicrobial drugs with a broad spectrum of antibacterial activity are frequently used in the treatment of various infections. Among these drugs, respiratory quinolones such as tosufloxacin, sparfloxacin and levofloxacin have been found to be particularly effective in treating most pneumococci, which are associated with respiratory tract infections. These respiratory quinolones have been demonstrated to have antibacterial effects against secondary infections after the induction of pulmonary damage caused by an influenza infection. In addition PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19734939 to antibacterial activity, it has been reported that FQs also function as an immunomodulator, an anti-oxidant agent and a nitric oxide regulator. These findings led us to conclude that FQs may have the potential to inhibit influenza virus-induced pneumonia via its pleiotropic effects, including its anti-oxidative and NO inhibitory properties. If that is the case, FQ would be expected to be, not only effective for the treatment of pulmonary damage associated with influenza virus infections, but also might inhibit the development of secondary infections caused by bacteria. The purpose of this study was to investigate the pleiotropic effects of LVFX, one of the most frequently used FQs, and to examine its therapeutic impact on the acute lung damage associated influenza virus infections using the PR8 influenza virus. To elucidate the mechanism responsible for the cytoprotective effect of LVFX on pulmonary damage, its anti-oxidant activities against ROS and NO in vitro and in vivo were evaluated using electron spin resonance spin PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19736622 trapping and immunohistochemical techniques. 2 / 16 Levofloxacin Protects against Influenza Virus-Induced Lung Injury Materials and Methods Animal Neuromedin N supplier ethics statement All animal experiments were approved by the experimental animal ethics committee at the Kumamoto University. All animal experiments were conducted in accordance with the guidelines of Kumamoto University for the care and use of laboratory animals. Materials 5, 5-dimethyl-1-pyrroline-N-oxide was purchased from Alexis Biochemicals. Ciprofloxacin, norfloxacin, pazfloxacin, levofloxacin, lomefloxacin and 1, 3-dimethylthiourea were purchased from Tokyo Chemical Industry Co., Ltd. Diethylenetriaminepentaacetic acid, NaNO2, N