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 proinflammatory 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-γ 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 5x107 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-α 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.
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