title: Antiviral effects of cyclosporine A in neonatal mice with rotavirus-induced diarrhea.
abstract: OBJECTIVE
  Because rotavirus gastroenteritis is associated with high morbidity and mortality especially in developing countries, it is necessary to develop antirotavirus drugs for the treatment of rotavirus infection. Previous studies have demonstrated that cyclosporin A (CsA) has antiviral properties against rotavirus. Its effect has not yet been evaluated against rotavirus diarrheal disease. The aim of this study was to assess the anti-rotavirus efficacy of CsA in neonatal mice after induction of rotavirus diarrhea.
  
  
  METHODS
  Suckling mice were inoculated with murine rotavirus. On the onset of diarrhea, mice were given different concentrations of CsA. To evaluate the effects of CsA on reduction of rotavirus diarrhea, diarrhea score, fecal virus shedding, and pathological lesion change in the small intestine, messenger RNA (mRNA) expression levels in the small intestine and spleen of mice were measured for type I interferon (IFN-α and IFN-β), inflammation-related cytokines (interleukin [IL]-8, IL-10, IFN-γ, and tumor necrosis factor-α), and inflammatory signaling pathways (p38, c-Jun N-terminal kinase, activator protein-1, and nuclear factor-kappa B).
  
  
  RESULTS
  Among virus-inoculated and CsA-treated groups, a dose of 5 mg · kg⁻¹ · day⁻¹ of CsA inhibited diarrhea and improved fecal virus shedding and intestinal lesion changes. IFN-β mRNA expression was significantly increased in rotavirus-induced diarrhea mice treated with 5 mg · kg⁻¹ · day⁻¹ of CsA, whereas the mRNA expression levels of inflammation-related cytokines (IL-8, IL-10, IFN-γ, and tumor necrosis factor-α) and inflammatory signaling pathways (p38, c-Jun N-terminal kinase, activator protein-1, and nuclear factor-kappa B) were markedly decreased. Antiviral effects of CsA were dose dependent.
  
  
  CONCLUSIONS
  CsA can inhibit rotavirus infection in neonatal mice through its antiviral properties. The mechanism for this may be through CsA suppression of inflammation by viral inhibition in animal models.
authors: Institute of Immunology, PLA, Third Military Medical University, Chongqing, PR China.
authors: Zigang
authors: Z
authors: Shen
authors: Zhiqiang
authors: Z
authors: Tian
authors: Haiyang
authors: H
authors: He
authors: Ji
authors: J
authors: Zhang
authors: Jintao
authors: J
authors: Li
authors: Yuzhang
authors: Y
authors: Wu
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D016572:Cyclosporine / Q000008:administration & dosage / Q000627:therapeutic use*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003967:Diarrhea / Q000209:etiology / Q000517:prevention & control*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005759:Gastroenteritis / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology / Q000821:virology; D005786:Gene Expression Regulation / Q000187:drug effects; D018836:Inflammation Mediators / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007421:Intestine, Small / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008807:Mice, Inbred BALB C; D011897:Random Allocation; D012401:Rotavirus / Q000187:drug effects* / Q000254:growth & development / Q000276:immunology / Q000302:isolation & purification; D012400:Rotavirus Infections / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology / Q000821:virology; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D017201:Virus Shedding / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D016207:Cytokines; D018836:Inflammation Mediators; D016572:Cyclosporine