Inhibitory effect of the TRFK-5 anti-IL-5 antibody in a guinea pig model of asthma.
To investigate the role of IL-5 in airway hyperreactivity and pulmonary eosinophilia, we used a model of allergic asthma in guinea pigs and a neutralizing monoclonal antibody (TRFK-5) directed against murine IL-5. Sensitized guinea pigs were challenged with 1% ovalbumin (OVA) aerosol and assessed for airway eosinophilia (by bronchoalveolar lavage [BAL] and histologic evaluation of airway tissue) and bronchoconstrictor responsiveness to substance P (SP) (as RL100 and Cdyn40) 24 h later. OVA challenge of sensitized animals caused a significant increase in airway responsiveness to SP, with a 4.9-fold decrease in RL100 and a 4.7-fold decrease in Cdyn40. Accompanying this increased sensitivity to SP was a 9-fold increase in eosinophils recovered in BAL and a 4- to 5-fold increase in eosinophils in intrapulmonary bronchial tissue. Intraperitoneal treatment with 10 mg/kg of the IL-5 antibody 2 h before OVA challenge blocked BAL and lung tissue increases in eosinophils but had no effect on the development of airway sensitivity to SP. In contrast, similar treatment with 30 mg/kg of this antibody blocked OVA-induced increased sensitivity to SP as well as BAL and lung tissue eosinophilia. These data suggest a critical and possibly independent role for IL-5 in allergic airway hyperresponsiveness and the accumulation of eosinophils within the lung of the guinea pig.
Mauser
P J
PJ
Schering-Plough Research Institute, Kenilworth, NJ 07033-0539.
Pitman
A
A
Witt
A
A
Fernandez
X
X
Zurcher
J
J
Kung
T
T
Jones
H
H
Watnick
A S
AS
Egan
R W
RW
Kreutner
W
W
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001249:Asthma / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016084:Bronchoconstriction / Q000502:physiology; D004804:Eosinophils / Q000473:pathology; D006168:Guinea Pigs; D007114:Immunization; D015848:Interleukin-5 / Q000276:immunology / Q000502:physiology*; D008168:Lung / Q000473:pathology; D008297:Male; D010047:Ovalbumin / Q000276:immunology; D013373:Substance P / Q000502:physiology
D000911:Antibodies, Monoclonal; D015848:Interleukin-5; D013373:Substance P; D010047:Ovalbumin