Therapeutic efficacy of an anti-IL-5 monoclonal antibody delivered into the respiratory tract in a murine model of asthma.
BACKGROUND
IL-5 is central to the pathogenesis of airway eosinophilic inflammation and hyperresponsiveness associated with both atopic and nonatopic asthma. The therapeutic potential of IL-5 antagonists in asthma is supported by the inhibition of airway eosinophilia and hyperresponsiveness in animal models receiving neutralizing anti-IL-5 mAbs intravenously or intraperitoneally.


OBJECTIVE
The purpose of this study was to test the hypothesis that mAbs against IL-5 delivered by way of the respiratory tract are as effective as those delivered intraperitoneally in diminishing the pulmonary eosinophilic inflammation and airway hyperresponsiveness in a murine model of ovalbumin-induced asthma.


METHODS
Ovalbumin-sensitized Balb/c mice were given an anti-IL-5 mAb delivered intranasally or an isotype-matched control mAb delivered intranasally before respiratory challenge with ovalbumin. Outcome variables included respiratory system resistance responses to methacholine, bronchoalveolar lavage fluid cellularity, and lung histopathology.


RESULTS
Anti-IL-5 mAbs administered intranasally to ovalbumin-sensitized and challenged mice significantly decreased eosinophil counts in bronchoalveolar lavage fluid and lung tissue and significantly reduced airway hyperresponsiveness relative to ovalbumin-sensitized and challenged mice that received either no mAb treatment or an isotype-matched control mAb. Similar results were obtained when an anti-IL-5 mAb was given intraperitoneally.


CONCLUSIONS
This is the first study to demonstrate that delivery of anti-IL-5 mAbs into the respiratory tract is efficacious in attenuating the asthma phenotype in a murine model. These results provide impetus for the development of inhaled IL-5 antagonists for the treatment of human asthma.
Departments of Pediatrics, Medicine, Pathology, and Microbiology and Immunology, Baylor College of Medicine, Houston, Texas, USA.
F R
FR
Shardonofsky
J
J
Venzor
R
R
Barrios
K P
KP
Leong
D P
DP
Huston
D000281:Administration, Intranasal; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001249:Asthma / Q000503:physiopathology*; D016535:Bronchial Hyperreactivity / Q000517:prevention & control; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004195:Disease Models, Animal; D006801:Humans; D007114:Immunization; D007274:Injections, Intraperitoneal; D015848:Interleukin-5 / Q000276:immunology*; D008168:Lung / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D012137:Respiratory System / Q000276:immunology*; D013810:Therapeutic Equivalency
D000911:Antibodies, Monoclonal; D015848:Interleukin-5; D010047:Ovalbumin