Inhibition of human interleukin-13-induced respiratory and oesophageal inflammation by anti-human-interleukin-13 antibody (CAT-354).
BACKGROUND
Allergic asthma is a complex disorder characterized by local and systemic T helper type 2 -cell responses such as the production of IL-13, a cytokine associated with the induction of airway hyper-responsiveness (AHR), chronic pulmonary eosinophilia, airway mucus overproduction and eosinophilic oesophagitis.


OBJECTIVE
Our study aimed to address the therapeutic potential of a human anti-human IL-13 IgG4 monoclonal antibody (CAT-354) in a murine model of respiratory and oesophageal inflammation induced by intratracheal human IL-13.


METHODS
BALB/c mice were treated on days 1 and 3 with CAT-354 (intraperitoneal injection), and human IL-13 was injected intratracheally on days 2 and 4. AHR to methacholine, airway eosinophilia in bronchoalveolar lavage fluid, histologic analysis of goblet cell metaplasia and oesophageal eosinophilia were evaluated.


RESULTS
Human IL-13 induced airway eosinophilia and goblet cell metaplasia in mice in a dose-dependent manner. Moreover, intratracheal dosing with 25 microg of human IL-13 was sufficient to induce AHR, goblet cell metaplasia and oesophageal eosinophilia. Pretreatment with CAT-354 significantly reduced AHR, airway eosinophilia and oesophageal eosinophilia.


CONCLUSIONS
These results demonstrate that anti-human IL-13 (CAT-354) is a potential therapeutic treatment for allergic airway and oesophageal diseases.
Blanchard
C
C
Department of Pediatrics, Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.
Mishra
A
A
Saito-Akei
H
H
Monk
P
P
Anderson
I
I
Rothenberg
M E
ME
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology*; D001249:Asthma / Q000276:immunology*; D004195:Disease Models, Animal; D004306:Dose-Response Relationship, Immunologic; D004802:Eosinophilia / Q000276:immunology; D004804:Eosinophils / Q000276:immunology; D004941:Esophagitis / Q000276:immunology*; D020397:Goblet Cells / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D018793:Interleukin-13 / Q000276:immunology*; D008168:Lung / Q000276:immunology / Q000473:pathology; D008679:Metaplasia; D051379:Mice; D008807:Mice, Inbred BALB C
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D018793:Interleukin-13