Efficacy of peroxisome proliferator activated receptor agonist in the treatment of virus-associated haemophagocytic syndrome in a rabbit model.
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.
Hsieh
Wen-Chuan
WC
Division of Infectious Diseases, National Health Research Institutes, Tainan, Taiwan.
Lan
Bau-Shin
BS
Chen
Yi-Ling
YL
Chang
Yao
Y
Chuang
Huai-Chia
HC
Su
Ih-Jen
IJ
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
D007004:Hypoglycemic Agents; D047495:PPAR gamma; D045162:Thiazolidinediones; D014409:Tumor Necrosis Factor-alpha; D000077154:Rosiglitazone