title: Efficacy of peroxisome proliferator activated receptor agonist in the treatment of virus-associated haemophagocytic syndrome in a rabbit model.
abstract: BACKGROUND
  Virus-associated haemophagocytic syndrome (VAHS) is a fatal complication of viral infections, such as Epstein-Barr virus and H5N1 influenza, that results from macrophage activation and pro inflammatory cytokine injuries. The high comorbidity and mortality of current therapy urgently demands an ideal agent based on VAHS pathogenesis. Peroxisome proliferator activated receptor (PPAR) agonists, regulators of metabolic syndrome, can exhibit immunomodulatory effects on macrophage activation and cytokine secretion.
  
  
  METHODS
  In this study, we adopted rosiglitazone, a PPAR-gamma agonist, for VAHS control in a Herpesvirus papio (HVP)-infected rabbit model. Various doses of rosiglitazone were orally administered to rabbits on day 7 or day 20 after intravenous challenge with 5 x 10(7) copies of HVP.
  
  
  RESULTS
  The rabbits that received 4 mg/day rosiglitazone had significantly increased survival when treated at an early stage of infection (P<0.01), whereas a higher dose (8 mg/day) was required at the advanced stage of the disease (P<0.05). All rosiglitazone-treated rabbits had significantly improved laboratory parameters and plasma tumour necrosis factor-alpha levels. Importantly, rosiglitazone could also inhibit viral replication in vitro and in vivo.
  
  
  CONCLUSIONS
  PPAR agonists could represent a potentially new agent for the therapy of VAHS.
authors.affiliation: Division of Infectious Diseases, National Health Research Institutes, Tainan, Taiwan.
authors.forename: Wen-Chuan
authors.initials: WC
authors.lastname: Hsieh
authors.forename: Bau-Shin
authors.initials: BS
authors.lastname: Lan
authors.forename: Yi-Ling
authors.initials: YL
authors.lastname: Chen
authors.forename: Yao
authors.initials: Y
authors.lastname: Chang
authors.forename: Huai-Chia
authors.initials: HC
authors.lastname: Chuang
authors.forename: Ih-Jen
authors.initials: IJ
authors.lastname: Su
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002144:Callithrix; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D006566:Herpesviridae Infections / Q000097:blood / Q000150:complications* / Q000821:virology; D004854:Herpesvirus 4, Human / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D051359:Lymphohistiocytosis, Hemophagocytic / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D047495:PPAR gamma / Q000819:agonists*; D011817:Rabbits; D000077154:Rosiglitazone; D018139:Simplexvirus / Q000187:drug effects / Q000502:physiology; D045162:Thiazolidinediones / Q000008:administration & dosage*; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D019562:Viral Load / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
chemical_list: D007004:Hypoglycemic Agents; D047495:PPAR gamma; D045162:Thiazolidinediones; D014409:Tumor Necrosis Factor-alpha; D000077154:Rosiglitazone