title: Combination of ribavirin and reduning protects mice against severe pneumonia induced by H1N1 influenza a virus.
abstract: OBJECTIVE
  To investigate the effects of ribavirin administration combined with Reduning in a mouse model of influenza A (H1N1)-induced severe pneumonia.
  
  
  METHODS
  Influenza A/Beijing/501/2009 (H1N1)-infected C57BL/6 mice were randomly divided into four experimental groups treated with either a mock injection of phosphate-buffered saline (PBS), ribavirin (66.6 mg/kg daily) or Reduning (86.6 mg/ kg daily), or a combination of both, for 7 days. Mice were monitored for clinical signs and survival, and body weight was measured daily for 14 days. Virus titer, lung wet-to-dry ratios, pathology and cytokines including interleukin (IL)-6, IL-10, and interferon (IFN)-γ were assayed on different days.
  
  
  RESULTS
  In the untreated group injected with phosphate buffer saline, all the mice died of the infection. The survival rate of mice treated with Reduning was only 10%, whereas 100% of the ribavirin- and the combination-treated mice survived. Low lung viral loads indicated that ribavirin significantly inhibited virus replication, whereas Reduning did not. Lung wet-to-dry ratios demonstrated that both ribavirin and Reduning, administered together or separately, reduced acute lung edema compared with results in the untreated group. Pathology analyses also showed that treatment with a combination of both drugs relieved pathological lesions, whereas the single drug treatment did not. Levels of IL-6, IL-10 and IFN-γ in mice treated with ribavirin or the combination of both ribavirin and Reduning were all significantly lower than in the untreated group, especially in the combination-treated group. In addition, Reduning administration significantly decreased both IL-6 and IL-10 production but had no effect on IFN-γ.
  
  
  CONCLUSIONS
  Due to the synergistic effect of antiviral and antiinflammation, the combination of ribavirin and Reduning could be an effective treatment for severe H1N1 which was considered to be significant to delayed antiviral and drug resistant.
authors.forename: Yuexia
authors.initials: Y
authors.lastname: Ma
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Zhongpeng
authors.initials: Z
authors.lastname: Zhao
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
authors.forename: Yuguang
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects / Q000502:physiology*; D007251:Influenza, Human / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000821:virology; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D011014:Pneumonia / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000821:virology; D012254:Ribavirin / Q000008:administration & dosage*
chemical_list: D000998:Antiviral Agents; D004365:Drugs, Chinese Herbal; D015850:Interleukin-6; C000596355:reduning; D016753:Interleukin-10; D012254:Ribavirin