Anti-IL-13 monoclonal antibody inhibits airway hyperresponsiveness, inflammation and airway remodeling.
Asthma is a chronic inflammatory disease characterized by reversible bronchial constriction, pulmonary inflammation and airway remodeling. Current standard therapies for asthma provide symptomatic control but fail to target the underlying disease pathology. Furthermore, no therapeutic agent is effective in preventing airway remodeling. Interleukin 13 (IL-13) is a pleiotropic cytokine produced mainly by T cells. A substantial amount of evidence suggests that IL-13 plays a critical role in the pathogenesis of asthma. Therefore, a neutralizing anti-IL-13 monoclonal antibody could provide therapeutic benefits to asthmatic patients. To test the concept we have generated a neutralizing rat anti-mouse IL-13 monoclonal antibody, and evaluated its effects in a chronic mouse model of asthma. Chronic asthma-like response was induced in ovalbumin (OVA) sensitized mice by repeated intranasal OVA challenges. After weeks of challenge, mice developed airway hyperresponsiveness (AHR) to methacholine stimulation, severe airway inflammation, hyper mucus production, and subepithelial fibrosis. When given at the time of each intranasal OVA challenge, anti-IL-13 antibody significantly suppressed AHR, eosinophil infiltration, proinflammatory cytokine/chemokine production, serum IgE, and most interestingly, airway remodeling. Taken together, these results strongly suggest that a neutralizing anti-human IL-13 monoclonal antibody could be an effective therapeutic agent for asthma.
Yang
Gaoyun
G
Centocor, Inc., 200 Great Valley Parkway, Malvern, PA 19355, USA.
Volk
Amy
A
Petley
Ted
T
Emmell
Eva
E
Giles-Komar
Jill
J
Shang
Xiaozhou
X
Li
Jian
J
Das
Anuk M
AM
Shealy
Dave
D
Griswold
Don E
DE
Li
Li
L
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D016085:Bronchoconstrictor Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007249:Inflammation / Q000188:drug therapy*; D018793:Interleukin-13 / Q000276:immunology*; D008168:Lung / Q000187:drug effects / Q000473:pathology; D016210:Methacholine Chloride / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D012137:Respiratory System / Q000187:drug effects*
D000911:Antibodies, Monoclonal; D016085:Bronchoconstrictor Agents; D018793:Interleukin-13; D016210:Methacholine Chloride