Antibody against interleukin-5 prevents antigen-induced eosinophil infiltration and bronchial hyperreactivity in the guinea pig airways.
Interleukin-5 (IL-5) induces proliferation, differentiation and activation of eosinophils. An animal model of local allergen (airways) sensitization was employed to study the effects of anti-IL-5 monoclonal antibody (mAb) on infiltration of eosinophils into inflammatory region, the development of antigen-induced late asthmatic response (LAR) and the increased bronchial responsiveness following LAR. Guinea pigs exposed to aerosolized ovalbumin (OVA) daily for 10 days developed an increase in the number of eosinophils in the tracheal wall 24 h after aerosolized OVA challenge. Furthermore, all animals developed an apparent LAR determined by the response with a 2-fold increase in respiratory resistance and showed an increase in bronchial responsiveness to acetylcholine 24 h after OVA challenge. In animals treated with anti-IL-5 mAb, however, eosinophil number in the tracheal wall dramatically decreased compared with animals treated with control antibody. The development of LAR was also remarkably suppressed by anti-IL-5 mAb treatment, although a similar magnitude of immediate bronchoconstriction was observed. Moreover, in anti-IL-5 antibody-treated guinea pigs, an increase in bronchial responsiveness to acetylcholine significantly decreased. Data demonstrate that IL-5 is involved in airway eosinophilia, development of LAR and an increase in bronchial responsiveness induced by allergen sensitization via the airways. Development of IL-5 synthesis inhibitors and/or receptor antagonists could provide another therapeutic class of anti-asthmatic drugs.
Akutsu
I
I
Department of Immunology, University of Tokyo, Japan.
Kojima
T
T
Kariyone
A
A
Fukuda
T
T
Makino
S
S
Takatsu
K
K
D000109:Acetylcholine / Q000494:pharmacology; D000336:Aerosols; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use*; D001249:Asthma / Q000150:complications* / Q000276:immunology / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000209:etiology / Q000517:prevention & control*; D001985:Bronchial Provocation Tests; D016084:Bronchoconstriction / Q000187:drug effects; D004802:Eosinophilia / Q000209:etiology / Q000517:prevention & control*; D006168:Guinea Pigs; D015848:Interleukin-5 / Q000037:antagonists & inhibitors* / Q000276:immunology; D007958:Leukocyte Count; D008168:Lung / Q000473:pathology; D008297:Male; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D013047:Specific Pathogen-Free Organisms; D014132:Trachea / Q000473:pathology
D000336:Aerosols; D000911:Antibodies, Monoclonal; D015848:Interleukin-5; D010047:Ovalbumin; D000109:Acetylcholine