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Research ArticleINFLAMMATION AND IMMUNOPHARMACOLOGY

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

Gaoyun Yang, Li Li, Amy Volk, Eva Emmell, Ted Petley, Jill Giles-Komar, Patricia Rafferty, Mani Lakshminarayanan, Don E. Griswold, Peter J. Bugelski and Anuk M. Das
Journal of Pharmacology and Experimental Therapeutics April 2005, 313 (1) 8-15; DOI: https://doi.org/10.1124/jpet.104.076133
Gaoyun Yang
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Li Li
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Amy Volk
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Eva Emmell
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Ted Petley
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Jill Giles-Komar
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Patricia Rafferty
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Mani Lakshminarayanan
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Don E. Griswold
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Peter J. Bugelski
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Anuk M. Das
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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 with 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.

Footnotes

  • This work was funded by Centocor Inc.

  • Part of this work was presented previously: Yang G, Li L, Volk A, Emmell E, Griswold DE, Bugelski PJ, and Das AM (2004) Therapeutic dosing with an anti-interleukin 13 (IL-13) monoclonal antibody is efficacious in a chronic murine model of asthma. Am J Respir Crit Care Med169:A699.

  • doi:10.1124/jpet.104.076133.

  • ABBREVIATIONS: IL, interleukin; rm, recombinant murine; AHR, airway hyperresponsiveness; STAT, signal transducer and activator of transcription; OVA, ovalbumin; mAb, monoclonal antibody; MMP-9, matrix metalloproteinase-9; PBS, phosphate-buffered saline; BAL, bronchoalveolar lavage; H&E, hematoxylin and eosin; PAS, periodic acid Schiff; SR, Sirius red; TNF, tumor necrosis factor.

    • Received August 17, 2004.
    • Accepted January 7, 2005.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 382 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 382, Issue 2
1 Aug 2022
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Research ArticleINFLAMMATION AND IMMUNOPHARMACOLOGY

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

Gaoyun Yang, Li Li, Amy Volk, Eva Emmell, Ted Petley, Jill Giles-Komar, Patricia Rafferty, Mani Lakshminarayanan, Don E. Griswold, Peter J. Bugelski and Anuk M. Das
Journal of Pharmacology and Experimental Therapeutics April 1, 2005, 313 (1) 8-15; DOI: https://doi.org/10.1124/jpet.104.076133

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Research ArticleINFLAMMATION AND IMMUNOPHARMACOLOGY

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

Gaoyun Yang, Li Li, Amy Volk, Eva Emmell, Ted Petley, Jill Giles-Komar, Patricia Rafferty, Mani Lakshminarayanan, Don E. Griswold, Peter J. Bugelski and Anuk M. Das
Journal of Pharmacology and Experimental Therapeutics April 1, 2005, 313 (1) 8-15; DOI: https://doi.org/10.1124/jpet.104.076133
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