Adenovirus-mediated blockade of tumor necrosis factor in mice protects against endotoxic shock yet impairs pulmonary host defense

Jay K. Kolls, Dinghua Lei, Steve Nelson, Warren R. Summer, Stanley Greenberg, Bruce Beutler

Research output: Contribution to journalArticle

83 Citations (Scopus)

Abstract

A replication-deficient recombinant adenovirus encoding a chimeric protein capable of binding tumor necrosis factor (TNF) and lymphotoxin was given to mice. Administration of this virus (109 pfu intravenously) yielded high levels of the recombinant protein in plasma and afforded significant protection to a lethal challenge with lipopolysaccharide with or without D- galactosamine. However, this protein inhibitor was readily detectable in the lung and was associated with decreased neutrophil recruitment and bacterial killing after intratracheal LPS or Pseudomonas aeruginosa, respectively. These data reflect the dual role of many proinflammatory cytokines. This model of TNF inhibition is similar to the homozygous 55-kDa TNF receptor deletion; thus, adenovirus-mediated gene transfer of cytokine inhibitors in vivo is a useful tool to abrogate the function of single or multiple cytokines for investigational or therapeutic purposes.

Original languageEnglish (US)
Pages (from-to)570-575
Number of pages6
JournalJournal of Infectious Diseases
Volume171
Issue number3
StatePublished - Mar 1995

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Septic Shock
Adenoviridae
Tumor Necrosis Factor-alpha
Cytokines
Lung
Lymphotoxin-alpha
Galactosamine
Neutrophil Infiltration
Recombinant Proteins
Protein Binding
Pseudomonas aeruginosa
Lipopolysaccharides
Viruses
Genes
Proteins
Therapeutics

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Immunology

Cite this

Adenovirus-mediated blockade of tumor necrosis factor in mice protects against endotoxic shock yet impairs pulmonary host defense. / Kolls, Jay K.; Lei, Dinghua; Nelson, Steve; Summer, Warren R.; Greenberg, Stanley; Beutler, Bruce.

In: Journal of Infectious Diseases, Vol. 171, No. 3, 03.1995, p. 570-575.

Research output: Contribution to journalArticle

Kolls, Jay K. ; Lei, Dinghua ; Nelson, Steve ; Summer, Warren R. ; Greenberg, Stanley ; Beutler, Bruce. / Adenovirus-mediated blockade of tumor necrosis factor in mice protects against endotoxic shock yet impairs pulmonary host defense. In: Journal of Infectious Diseases. 1995 ; Vol. 171, No. 3. pp. 570-575.
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