help button home button
AJRCCM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
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 Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by KOLB, M.
Right arrow Articles by GAULDIE, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by KOLB, M.
Right arrow Articles by GAULDIE, J.

Am. J. Respir. Crit. Care Med., Volume 164, Number 5, September 2001, 866-872

Budesonide Enhances Repeated Gene Transfer and Expression in the Lung with Adenoviral Vectors

MARTIN KOLB, MARK INMAN, PETER J. MARGETTS, TOM GALT, and JACK GAULDIE

Department of Pathology and Molecular Medicine and Centre for Gene Therapeutics, and Department of Medicine, McMaster University, Hamilton, Ontario, Canada; and Medizinische Klinik, Julius-Maximilians-Universität Würzburg, Germany

The immune response with generation of neutralizing antiviral antibodies is an obstacle to effective repeated adenoviral gene transfer. Different immunosuppressive drugs facilitate repeat administration of adenovectors, but the clinical utility is uncertain because of systemic side effects. We investigated the use of topical corticosteroid in improving gene expression after repeated injection of adenovectors into mouse lungs. Using a vector expressing murine interleukin-6 (mIL-6) as a marker cytokine for gene expression, we show that budesonide given around exposure to adenovirus to the lung significantly maintained high levels of expressed transgene protein in bronchoalveolar lavage fluid (BALF) after as many as four consecutive injections of virus at two weekly intervals (p = 0.02 versus saline). Differences between treatment groups were most obvious 4 and 6 wk after the initial exposure to adenovirus (equivalent to three and four total exposures). In Week 4, transgene mIL-6 concentration was 2,327 ± 955 pg/ml in budesonide compared with 336 ± 246 pg/ml in saline-treated mice (p = 0.001). However, budesonide did not significantly protect transgene expression beyond Week 8 (four prior exposures). The improved transgene expression in budesonide-treated compared with saline-treated animals was associated with a reduction, but not prevention of neutralizing antiviral antibodies (BALF p < 0.001, serum p = 0.04). We conclude that budesonide can be valuable in gene therapy of the lung where repeated transient gene transfer is necessary.

Keywords: adenoviral gene transfer; gene expression; budesonide




This article has been cited by other articles:


Home page
 Cancer Res.Home page
M. J. Wilderman, J. Sun, A. S. Jassar, V. Kapoor, M. Khan, A. Vachani, E. Suzuki, P. A. Kinniry, D. H. Sterman, L. R. Kaiser, et al.
Intrapulmonary IFN-{beta} Gene Therapy Using an Adenoviral Vector Is Highly Effective in a Murine Orthotopic Model of Bronchogenic Adenocarcinoma of the Lung
Cancer Res., September 15, 2005; 65(18): 8379 - 8387.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
R. E. Wiley, M. Cwiartka, D. Alvarez, D. C. Mackenzie, J. R. Johnson, S. Goncharova, L. Lundblad, and M. Jordana
Transient Corticosteroid Treatment Permanently Amplifies the Th2 Response in a Murine Model of Asthma
J. Immunol., April 15, 2004; 172(8): 4995 - 5005.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
C. S. Robbins, D. E. Dawe, S. I. Goncharova, M. A. Pouladi, A. G. Drannik, F. K. Swirski, G. Cox, and M. R. Stampfli
Cigarette Smoke Decreases Pulmonary Dendritic Cells and Impacts Antiviral Immune Responsiveness
Am. J. Respir. Cell Mol. Biol., February 1, 2004; 30(2): 202 - 211.
[Abstract] [Full Text] [PDF]

Home page
 J. Thorac. Cardiovasc. Surg.Home page
T. Suda, T. Tagawa, S. A. Kanaan, B. D. Kozower, N. Daddi, T. Mohanakumar, and G. A. Patterson
Adenovirus encoding soluble tumor necrosis factor {alpha} receptor immunoglobulin prolongs gene expression of a cotransfected reporter gene in rat lung
J. Thorac. Cardiovasc. Surg., October 1, 2003; 126(4): 1155 - 1161.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
M. J. Tobin
Compliance (COMmunicate PLease wIth Less Abbreviations, Noun Clusters, and Exclusiveness)
Am. J. Respir. Crit. Care Med., December 15, 2002; 166(12): 1534 - 1536.
[Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
M. J. TOBIN
Asthma, Airway Biology, and Nasal Disorders in AJRCCM 2001
Am. J. Respir. Crit. Care Med., March 1, 2002; 165(5): 598 - 618.
[Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
P. J. Margetts, S. Gyorffy, M. Kolb, L. Yu, C. M. Hoff, C. J. Holmes, and J. Gauldie
Antiangiogenic and Antifibrotic Gene Therapy in a Chronic Infusion Model of Peritoneal Dialysis in Rats
J. Am. Soc. Nephrol., March 1, 2002; 13(3): 721 - 728.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Proc. Am. Thorac. Soc. Am. J. Respir. Cell Mol. Biol.
Copyright © 2001 American Thoracic Society