JPET Introducing ALZET?ew Model 2006 Pump

Home Help [Feedback] [For Subscribers] [Archive] [Search] --
QUICK SEARCH:   [advanced]


     

Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on January 11, 2005; DOI: 10.1124/jpet.104.076133

This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
jpet.104.076133v1
313/1/8    most recent
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
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
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Yang, G.
Right arrow Articles by Das, A. M
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Yang, G.
Right arrow Articles by Das, A. M


Received for publication August 17, 2004.
Revised December 9, 2004.
Accepted for publication January 7, 2005.

Therapeutic Dosing with Anti-Interleukin-13 Monoclonal Antibody Inhibits Asthma Progression in Mice

Gaoyun Yang 1, Li Li 1, Amy Volk 1, Eva Emmell 1, Ted Petley 1, Jill Giles-Komar 1, Patricia Rafferty 1, Mani Lakshminaryanan 1, Don E Griswold 1, Peter J Bugelski 1, Anuk M Das 1*

1 Centocor

* Address correspondence to: E-mail: adas2{at}cntus.jnj.com

Abstract

In vivo models have demonstrated that interleukin-13 (IL-13) plays an important role in asthma. However, few studies have evaluated the effect of inhibition of IL-13 on established and persistent disease. In the present study we have investigated the effect of a therapeutic dosing regimen with an anti-IL-13 monoclonal antibody (mAb) in a chronic mouse model of persistent asthma. Balb/c mice were sensitized to allergen (ovalbumin, OVA, on days 1 and 8) and challenged with OVA weekly from day 22. Anti-IL-13 mAb or vehicle dosing was initiated following two OVA challenges when disease was established. At this time, mice exhibited airway hyperresponsiveness (AHR), increased mucus production, inflammation and initiation of subepithelial fibrosis compared to saline-challenged mice. Mice received four additional OVA challenges. Treatment with anti-IL-13 mAb inhibited AHR and prevented the further development of subepithelial fibrosis and progression of inflammation. Furthermore, mAb treatment reversed the mucus hyperplasia to basal levels. These effects were associated with an inhibition of cytokines, chemokines and matrix metalloproteinase-9. These data demonstrate that neutralization of IL-13 can inhibit the progression of established disease in the presence of repeated allergen exposures.


Key words: IL-13, asthma, disease progression, in vivo, monoclonal antibody, pathology


This article has been cited by other articles:


Home page
 Am. J. Respir. Crit. Care Med.Home page
Y. Ma, K. T. HayGlass, A. B. Becker, Y. Fan, X. Yang, S. Basu, G. Srinivasan, F. E. R. Simons, A. J. Halayko, and Z. Peng
Novel Recombinant Interleukin-13 Peptide-based Vaccine Reduces Airway Allergic Inflammatory Responses in Mice
Am. J. Respir. Crit. Care Med., September 1, 2007; 176(5): 439 - 445.
[Abstract] [Full Text] [PDF]

Home page
 Eur Respir JHome page
C. M. Lloyd and D. S. Robinson
Allergen-induced airway remodelling
Eur. Respir. J., May 1, 2007; 29(5): 1020 - 1032.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
J. G. Karras, J. R. Crosby, M. Guha, D. Tung, D. A. Miller, W. A. Gaarde, R. S. Geary, B. P. Monia, and S. A. Gregory
Anti-Inflammatory Activity of Inhaled IL-4 Receptor-{alpha} Antisense Oligonucleotide in Mice
Am. J. Respir. Cell Mol. Biol., March 1, 2007; 36(3): 276 - 285.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
S. Wenzel and S. T. Holgate
The Mouse Trap: It Still Yields Few Answers in Asthma
Am. J. Respir. Crit. Care Med., December 1, 2006; 174(11): 1173 - 1176.
[Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] --
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 2005 by the American Society for Pharmacology and Experimental Therapeutics.