title: Combinations of oseltamivir and fibrates prolong the mean survival time of mice infected with the lethal H7N9 influenza virus.
abstract: The outbreak of human infections caused by the novel avian-origin H7N9 influenza viruses in China since March 2013 underscores the urgent need to find an effective treatment strategy against H7N9 infection in humans. In this study, we assessed the effectiveness of combinations of oseltamivir and two immunomodulators (simvastatin and fenofibrate) against H7N9 infection in a mouse model. Mice treated with oseltamivir plus fenofibrate exhibited the longest mean survival time, the largest reduction of viral titre in lung tissue, the highest levels of CD4(+) and CD8(+) T-lymphocytes, and the greatest decrease in pulmonary inflammation. Thus, the combination of oseltamivir plus fenofibrate improved the outcomes of mice infected with H7N9 virus by simultaneously reducing viral replication and normalizing the aberrant immune response. This drug combination should be considered in randomized controlled trials of treatments for H7N9 patients.
authors.affiliation: Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) and Comparative Medicine Center, Peking Union Medical College (PUMC), Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Beijing, PR China.
authors.forename: Lili
authors.initials: L
authors.lastname: Xu
authors.affiliation: Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) and Comparative Medicine Center, Peking Union Medical College (PUMC), Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Beijing, PR China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Bao
authors.affiliation: Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) and Comparative Medicine Center, Peking Union Medical College (PUMC), Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Beijing, PR China.
authors.forename: Fengdi
authors.initials: F
authors.lastname: Li
authors.affiliation: Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) and Comparative Medicine Center, Peking Union Medical College (PUMC), Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Beijing, PR China.
authors.forename: Songzhi
authors.initials: S
authors.lastname: Gu
authors.affiliation: Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) and Comparative Medicine Center, Peking Union Medical College (PUMC), Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Beijing, PR China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Lv
authors.affiliation: Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) and Comparative Medicine Center, Peking Union Medical College (PUMC), Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Beijing, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yuan
authors.affiliation: Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) and Comparative Medicine Center, Peking Union Medical College (PUMC), Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Beijing, PR China.
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) and Comparative Medicine Center, Peking Union Medical College (PUMC), Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Beijing, PR China.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) and Comparative Medicine Center, Peking Union Medical College (PUMC), Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Beijing, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Deng
authors.affiliation: Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) and Comparative Medicine Center, Peking Union Medical College (PUMC), Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Beijing, PR China.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Li
authors.affiliation: Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) and Comparative Medicine Center, Peking Union Medical College (PUMC), Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Beijing, PR China.
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) and Comparative Medicine Center, Peking Union Medical College (PUMC), Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Beijing, PR China.
authors.forename: Pin
authors.initials: P
authors.lastname: Yu
authors.affiliation: Department of Respiratory and Critical Care Medicine, Peking University People's Hospital, Beijing, PR China.
authors.forename: Zhancheng
authors.initials: Z
authors.lastname: Gao
authors.affiliation: Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) and Comparative Medicine Center, Peking Union Medical College (PUMC), Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Beijing, PR China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Qin
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D058607:Fibric Acids / Q000494:pharmacology*; D064766:Influenza A Virus, H7N9 Subtype / Q000187:drug effects*; D008168:Lung / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000188:drug therapy*; D053139:Oseltamivir / Q000494:pharmacology*; D013534:Survival; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D058607:Fibric Acids; D053139:Oseltamivir