Systemic interleukin-6 responses following administration of adenovirus gene transfer vectors to humans by different routes. Academic Article uri icon

Overview

MeSH

  • Aged
  • Animals
  • Antibodies, Viral
  • Colonic Neoplasms
  • Coronary Artery Disease
  • Cystic Fibrosis
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Cytosine Deaminase
  • Endothelial Growth Factors
  • Escherichia coli
  • Female
  • Genes, Bacterial
  • Humans
  • Liver Neoplasms
  • Lymphokines
  • Male
  • Middle Aged
  • Neutralization Tests
  • Nucleoside Deaminases
  • Peripheral Vascular Diseases
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors

MeSH Major

  • Adenoviridae
  • Genetic Therapy
  • Genetic Vectors
  • Interleukin-6

abstract

  • Administration of adenovirus (Ad) vectors to animals induces innate immune responses, typified by elevated interleukin-6 (IL-6). To assess innate responses to Ad vectors in humans, we evaluated serum IL-6 following administration of E1(-) E3(-) Ad vectors to different human hosts and the relationship among peak IL-6 and peak anti-Ad neutralizing antibodies. We administered: 1) Ad(GV)CFTR.10, a vector carrying the normal human CFTR cDNA (3 x 10(7) to 2 x 10(10) particle units (pu)) to airways of individuals with cystic fibrosis (CF); 2) Ad(GV)VEGF121.10, a vector carrying the normal human vascular endothelial growth factor (VEGF)121 cDNA, to the myocardium (4 x 10(8) to 4 x 10(10) pu) of individuals with coronary artery disease (CAD) and to lower extremity muscles (4 x 10(8) to 4 x 10(9.5) pu) of individuals with peripheral vascular disease (PVD); and 3) Ad(GV)CD.10, a vector carrying the Escherichia coli cytosine deaminase gene to skin (7 x 10(7) to 7 x 10(9) pu) and airways (7 x 10(8) to 7 x 10(10) pu) of normal individuals and to liver metastasis (4 x 10(8) to 4 x 10(9) pu) of individuals with colon carcinoma. IL-6 increased mildly (up to 220 pg/ml) following vector administration to skin and lung airways of normal individuals and of individuals with CF, and to muscle and liver metastasis of individuals with PVD and colon cancer, respectively. IL-6 responses were higher (up to 1100 pg/ml) following myocardial administration. Control individuals who had chest surgery and bronchoscopy, but no vector administration, had comparable IL-6 increases. Thus, both administration of Ad vectors of humans up to 10(10) pu and the procedures used to administer the vectors elicit systemic IL-6 responses. There was no correlation among peak IL-6 and peak anti-Ad antibodies. These observations indicate that the innate host responses following administration of Ad vectors to humans may result from the procedures used to administer the vector, and from the vector per se.

publication date

  • August 2002

has subject area

  • Adenoviridae
  • Aged
  • Animals
  • Antibodies, Viral
  • Colonic Neoplasms
  • Coronary Artery Disease
  • Cystic Fibrosis
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Cytosine Deaminase
  • Endothelial Growth Factors
  • Escherichia coli
  • Female
  • Genes, Bacterial
  • Genetic Therapy
  • Genetic Vectors
  • Humans
  • Interleukin-6
  • Liver Neoplasms
  • Lymphokines
  • Male
  • Middle Aged
  • Neutralization Tests
  • Nucleoside Deaminases
  • Peripheral Vascular Diseases
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors

Research

keywords

  • Clinical Trial
  • Controlled Clinical Trial
  • Journal Article

Identity

Language

  • eng

PubMed ID

  • 12349828

Additional Document Info

start page

  • 287

end page

  • 297

volume

  • 6

number

  • 2