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INFLAMMATION AND IMMUNOPHARMACOLOGY

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

Immunobiology (G.Y., L.L., D.E.G., A.M.D.), Toxicology and Investigational Pharmacology (A.V., E.E., P.R., P.J.B.), Cellular Biology (T.P., J.G.-K.), and Biostatistics (M.L.), Centocor Inc., Radnor, Pennsylvania

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.

Address correspondence to: Dr. Anuk M. Das, Immunobiology, Centocor Inc., Mail Stop: R-4-1, 145 King of Prussia Rd., Radnor, PA 19087. E-mail: adas2{at}cntus.jnj.com

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