Therapeutic efficacy of an anti–IL-5 monoclonal antibody delivered into the respiratory tract in a murine model of asthma Felix R. Shardonofsky, MD,

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Therapeutic efficacy of an anti–IL-5 monoclonal antibody delivered into the respiratory tract in a murine model of asthma Felix R. Shardonofsky, MD, Joe Venzor, MD, Roberto Barrios, MD, Khai-Pang Leong, MD, David P. Huston, MD Journal of Allergy and Clinical Immunology Volume 104, Issue 1, Pages 215-221 (July 1999) DOI: 10.1016/S0091-6749(99)70138-7 Copyright © 1999 Mosby, Inc. Terms and Conditions

Fig. 1 Number of leukocytes (A) and differential of leukocytes (B) in BALF obtained from sham-sensitized and challenged mice (n = 9), ovalbumin-sensitized and challenged mice that either were not treated with mAb (n = 10) or were treated with anti–IL-5 mAb (TRFK-5) intranasally (n = 11) or intraperitoneally (n = 10), and from ovalbumin-sensitized and challenged mice treated with an isotype-matched control mAb (GL-113; n = 10). Data are expressed as the means ± SEM of number of cells · mm -3 (A) and percentage of leukocyte subpopulations (B) . ANOVA followed by Tukey’s test: * Different from sham-sensitized and challenged mice ( P < .05); § different from ovalbumin-sensitized and challenged mice either not treated with mAb or treated with GL-113 mAb ( P < .05). Journal of Allergy and Clinical Immunology 1999 104, 215-221DOI: (10.1016/S0091-6749(99)70138-7) Copyright © 1999 Mosby, Inc. Terms and Conditions

Fig. 2 Lung histopathology. A , Lung section from a sham-sensitized and challenged mouse shows bronchioli, small pulmonary vessels, and alveoli with no evidence of inflammation. B , Lung section from an ovalbumin-sensitized mouse shows prominent inflammatory cell infiltrates composed of eosinophils, macrophages, and lymphocytes surrounding bronchioli and vessels. Patchy alveolar inflammatory cell infiltrates are seen. Inflammatory cells and debris are observed within the airway lumen. C , Lung section from an ovalbumin-sensitized mouse treated intranasally with an anti–IL-5 mAb (TRFK-5). There is a marked decrease of the intensity of inflammatory infiltrate in comparison with that seen in the ovalbumin-sensitized animal that received no mAb treatment ( B ). D , Lung section from an ovalbumin-sensitized and challenged mouse treated intranasally with an isotype-matched control mAb (GL-113). Peribronchiolar and perivascular inflammatory changes are similar to those observed in the ovalbumin-sensitized and challenged mouse that received no mAb treatment ( B ). Lungs were fixed after BAL was performed. (Hematoxylin and eosin stain; original magnification: ×35.) Journal of Allergy and Clinical Immunology 1999 104, 215-221DOI: (10.1016/S0091-6749(99)70138-7) Copyright © 1999 Mosby, Inc. Terms and Conditions

Fig. 3 Lung histopathology. A , Lung section from a sham-sensitized and challenged mouse shows no inflammatory changes. B , Lung section from an ovalbumin-sensitized mouse. Inflammatory cells, including eosinophils, macrophages, and lymphocytes, infiltrate the interstitium and adventitia of a bronchiole. The latter contains debris within its lumen. C , Lung section from an ovalbumin-sensitized mouse treated intranasally with an anti–IL-5 mAb (TRFK-5). The magnitude of the peribronchiolar inflammatory cellular infiltrate is substantially decreased relative to that observed in the ovalbumin-sensitized and challenged mouse that received no mAb treatment( B ). D , Lung section from an ovalbumin-sensitized and challenged mouse treated intranasally with an isotype-matched control mAb (GL-113). A bronchiole whose lumen is filled with mucus is encased by a dense inflammatory infiltrate similar to that seen in ovalbumin-sensitized and challenged mice that received no mAb treatment ( B ). Lungs were fixed after bronchoalveolar lavage was performed. (Hematoxylin and eosin stain; original magnification, ×70.) Journal of Allergy and Clinical Immunology 1999 104, 215-221DOI: (10.1016/S0091-6749(99)70138-7) Copyright © 1999 Mosby, Inc. Terms and Conditions

Fig. 4 Number of leukocytes in lung tissue. Data are expressed as means ± SEM of number of eosinophils ( A ), lymphocytes ( B ), and macrophages ( C ) per high-power field (original magnification, ×450) in bronchi ( Br ), bronchioli ( Bl ), alveoli ( Alv ), and perivascular tissues ( PeriV ) of the lungs from sham-sensitized and challenged mice (n = 9) from ovalbumin-sensitized and challenged mice that either were not treated with mAb (n = 10) or were treated with anti–IL-5 mAb (TRFK-5) intranasally (n = 11) or intraperitoneally ( ip ; n = 10), and from ovalbumin-sensitized mice treated with an isotype-matched control mAb (GL-113; n = 10). ANOVA followed by Tukey’s test: * Different from sham-sensitized and challenged mice ( P < .05) and different from nonsensitized mice ( P < .05); § different from ovalbumin-sensitized and challenged mice not treated with mAb or treated with GL-113 mAb ( P < .05). Journal of Allergy and Clinical Immunology 1999 104, 215-221DOI: (10.1016/S0091-6749(99)70138-7) Copyright © 1999 Mosby, Inc. Terms and Conditions

Fig. 5 Effects of anti–IL-5 mAb on airway responsiveness to methacholine. Data are expressed as means ± SEM of methacholine dose/airway response relationships using Rrs as an index of airway caliber from sham-sensitized and challenged mice (n = 9), ovalbumin-sensitized and challenged mice that either were not treated with mAb (n = 10) or were treated with anti–IL-5 mAb (TRFK-5) intranasally (n = 11) or intraperitoneally (n = 10), and from ovalbumin-sensitized and challenged mice treated with an isotype-matched control mAb (GL-113; n = 10). S indicates administration of saline solution. ANOVA followed by Tukey’s test: * Different from sham-sensitized and challenged mice ( P < .05) and different from nonsensitized mice ( P < .05); § different from ovalbumin-sensitized and challenged mice not treated with mAb or treated with GL-113 mAb ( P < .05). ip , Intraperitoneally. Journal of Allergy and Clinical Immunology 1999 104, 215-221DOI: (10.1016/S0091-6749(99)70138-7) Copyright © 1999 Mosby, Inc. Terms and Conditions