國家衛生研究院 NHRI:Item 3990099045/4599

NHRI > National Institute of Infectious Diseases and Vaccinology > Ih-Jen Su(2002-2015) > Conference Papers/Meeting Abstract > Item 3990099045/4599

Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/4599

Title:	Control of EBV-associated hemophagocytic syndrome by peroxisome proliferator activated receptor agonist
Authors:	Su, IJ
Contributors:	Division of Infectious Diseases
Abstract:	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.
Date:	2009-10
Relation:	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
Appears in Collections:	[Ih-Jen Su(2002-2015)] Conference Papers/Meeting Abstract

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