First-generation adenovirus vectors shorten survival time in a murine model of sepsis

Kevin Doerschug; Salih Sanlioglu; Dawn M Flaherty; Rebecca L Wilson; Timur Yarovinsky; Martha M Monick; John F Engelhardt; Gary W Hunninghake

doi:10.4049/jimmunol.169.11.6539

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First-generation adenovirus vectors shorten survival time in a murine model of sepsis

Journal article

Peer reviewed

First-generation adenovirus vectors shorten survival time in a murine model of sepsis

Kevin Doerschug, Salih Sanlioglu, Dawn M Flaherty, Rebecca L Wilson, Timur Yarovinsky, Martha M Monick, John F Engelhardt and Gary W Hunninghake

The Journal of immunology (1950), Vol.169(11), pp.6539-6545

12/01/2002

DOI: 10.4049/jimmunol.169.11.6539

PMID: 12444165

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Abstract

Adverse immunological reactions to adenoviral vectors have significantly impacted the utility of this virus for treating genetic and environmentally induced diseases. In this study, we evaluate the effect of adenoviral vectors on an animal model of sepsis. Systemic delivery of first-generation adenoviral vectors to septic mice (cecal ligation and puncture) resulted in a shortened survival time. This effect was not observed with second-generation or inactivated first-generation vectors. The accelerated death was accompanied by a number of important changes in the disease. These changes included increased liver cell apoptosis (including Kupffer cells) and a marked increase in liver bacterial load. In the lung, the combination induced an increase in bacterial load, as well as greater lung injury. In the serum, the combination was associated with decreased TNF-alpha levels and an increase in bacterial load. Finally, a profound degree of lymphocyte apoptosis was observed in these animals. These observations suggest that prior exposure to first-generation adenovirus gene therapy vectors may worsen the outcome of some forms of sepsis.

Tumor Necrosis Factor-alpha - metabolism

Kupffer Cells - pathology

Lung - microbiology

Liver - pathology

Lung - pathology

Sepsis - immunology

Mice, Inbred C57BL

Liver - microbiology

Colony Count, Microbial

Lymphocytes - pathology

Animals

Sepsis - pathology

Sepsis - therapy

Thymus Gland - pathology

Adenoviridae - genetics

Female

Mice

Safety

Genetic Vectors

Spleen - pathology

Genetic Therapy - adverse effects

Genetic Therapy - methods

Details

Title: Subtitle: First-generation adenovirus vectors shorten survival time in a murine model of sepsis
Creators: Kevin Doerschug - Division of Pulmonary, Critical Care and Occupational Medicine, Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242, USA. kevin-doerschug@uiowa.edu
Salih Sanlioglu
Dawn M Flaherty
Rebecca L Wilson
Timur Yarovinsky
Martha M Monick
John F Engelhardt
Gary W Hunninghake
Resource Type: Journal article
Publication Details: The Journal of immunology (1950), Vol.169(11), pp.6539-6545
DOI: 10.4049/jimmunol.169.11.6539
PMID: 12444165
NLM abbreviation: J Immunol
ISSN: 0022-1767
eISSN: 1550-6606
Publisher: United States
Grant note: HL-60316 / NHLBI NIH HHS P30 DK54759 / NIDDK NIH HHS ES-09607 / NIEHS NIH HHS
Language: English
Date published: 12/01/2002
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Pulmonary, Critical Care, and Occupational Medicine; Anatomy and Cell Biology; Radiation Oncology; Internal Medicine
Record Identifier: 9984025437502771

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