PT  - JOURNAL ARTICLE
AU  - Gaoyun Yang
AU  - Li Li
AU  - Amy Volk
AU  - Eva Emmell
AU  - Ted Petley
AU  - Jill Giles-Komar
AU  - Patricia Rafferty
AU  - Mani Lakshminarayanan
AU  - Don E. Griswold
AU  - Peter J. Bugelski
AU  - Anuk M. Das
TI  - Therapeutic Dosing with Anti-Interleukin-13 Monoclonal Antibody Inhibits Asthma Progression in Mice
AID  - 10.1124/jpet.104.076133
DP  - 2005 Apr 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 8--15
VI  - 313
IP  - 1
4099  - http://jpet.aspetjournals.org/content/313/1/8.short
4100  - http://jpet.aspetjournals.org/content/313/1/8.full
SO  - J Pharmacol Exp Ther2005 Apr 01; 313
AB  - 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. The American Society for Pharmacology and Experimental Therapeutics