Advanced Search

Journal Navigation

Journal Home

Subscriptions

Archive

Contact Us

Table of Contents

Sign In to gain access to subscriptions and/or personal tools.
Journal of Endotoxin Research
This Article
Right arrow Full Text (PDF)
Right arrow References
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Saved Citations
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Request Reprints
Right arrow Add to My Marked Citations
Citing Articles
Right arrow Citing Articles via Google Scholar
Right arrow Citing Articles via Scopus
Google Scholar
Right arrow Articles by Oberholzer, C.
Right arrow Articles by Moldawer, L. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Oberholzer, C.
Right arrow Articles by Moldawer, L. L.
Right arrowPubmed/NCBI databases
*Compound via MeSH
*Substance via MeSH
Medline Plus Health Information
*Genes and Gene Therapy
*Liver Diseases
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Influence of recombinant adenovirus on liver injury in endotoxicosis and its modulation by IL-10 expression

Caroline Oberholzer

Department of Surgery, University of Florida College of Medicine, Gainesville, Florida, USA

Andreas Oberholzer

Department of Surgery, University of Florida College of Medicine, Gainesville, Florida, USA

Sven K. Tschoeke

Department of Surgery, University of Florida College of Medicine, Gainesville, Florida, USA

Rebecca M. Minter

Department of Surgery, University of Florida College of Medicine, Gainesville, Florida, USA

Frances R. Bahjat

Department of Surgery, University of Florida College of Medicine, Gainesville, Florida, USA

Drake LaFace

Canjii Inc., San Diego, California, USA

Beth Hutchins

Canjii Inc., San Diego, California, USA

Lyle L. Moldawer

Department of Surgery, University of Florida College of Medicine, Gainesville, Florida, USA, moldawer{at}surgery.ufl.edu

Adenovirus-based gene therapy offers a unique opportunity to target gene expression to the liver by systemic delivery. However, systemic administration of a first generation adenoviral construct elicits an inflammatory response leading to TNF-{alpha}-dependent liver injury. The aim of this study was to evaluate whether the systemic administration of recombinant adenovirus exacerbates a subsequent TNF-{alpha}-dependent liver injury induced by D-galactosamine and lipopolysaccharide. Surprisingly, low-dose adenovirus administration (105 particles) protects, while high-dose adenovirus (1010 particles) is associated with an exaggerated hepatic inflammatory response from a subsequent D-galactosamine and lipopolysaccharide challenge. This exacerbation is TNF-{alpha} dependent, since treatment with a TNF inhibitor fully protects against the liver injury. Moreover, intravenous administration of an adenoviral construct expressing the anti-inflammatory protein interleukin-10 reduces TNF-{alpha} appearance and attenuates the increased hepatocyte injury. Taken together, this report demonstrates potential additive effects of TNF-{alpha} responses induced by adenovirus and other inflammatory signals, and suggests that the response can be mitigated by relative adenovirus particle dose or by inhibitors, such as TNF-binding protein or interleukin 10.

Key Words: Gene therapy • inflammation • apoptosis • cytokine • lipopolysaccharide

Journal of Endotoxin Research, Vol. 10, No. 6, 393-401 (2004)
DOI: 10.1177/09680519040100060301
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?