國家衛生研究院 NHRI:Item 3990099045/4599
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    題名: Control of EBV-associated hemophagocytic syndrome by peroxisome proliferator activated receptor agonist
    作者: Su, IJ
    貢獻者: Division of Infectious Diseases
    摘要: Hemophagocytic syndrome (HPS) or hemopahgocytic lymphohistiocytosis (HLH) is afatal complication associated with severe viral infections, genetic disorders, ormalignancies. The pathogenesis of HPS is presumed to result from an enhancedproinflammatory cytokine secretion and systemic macrophage activation, resulting insystemic organ damages. In the past years, our group worked on the pathogenesis ofHPS and clarified that NFkB-mediated T cell and macrophage activation is the majormechanism. Therapy targeted at the pathogenic signaling pathways of HPS usingdrugs having minimal side effects is desirable. Since peroxisome proliferatorsactivated receptor (PPAR) agonists, regulators of cholesterol metabolism, have beenshown to exhibit profound effects on the inhibition of proinflammatory cytokines andmacrophage activation through NFkB or AP-I pathway, rosiglitazone, a PPAR-gammaagonist, was tested for treatment of HPS using a rabbit model of Herpesvirus papio(HVP, an EBV homologue)-associated HPS. In vitro, rosiglitazone was shown toinhibit macrophage activation and secretion of tumor necrosis factor-alpha throughinhibition of NFkB signaling in the U937 cell line. Different doses of rosiglitazonewere fed to rabbits after intravenous injection of 5 107 copies of HVP virus atdifferent time courses (7 and 20 days, respectively) of infection. As compared to thecontrol group which succumbed consistently at around one month, the 4 mgrosiglitazone-treated group showed significant improvement of survival when fed atan early stage (7 days) of infection (p < 0.01), while a higher dosage (8 mg) is neededto achieve therapeutic effect at advanced stage (20 days) of diseases (p < 0.05). Theviral load, TNF-alpha cytokine levels, and laboratory parameters also showedsignificant improvement in the rosiglitazone-treated group. PPAR agonists appear tobe active within model and should be considered for further clinical testing.
    日期: 2009-10
    關聯: Pediatric Blood & Cancer. 2009 Oct;53(4):688.
    Link to: http://dx.doi.org/10.1002/pbc.22235
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1545-5009&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000269295500048
    顯示於類別:[蘇益仁(2002-2015)] 會議論文/會議摘要

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