Involvement of IL-5 in a murine model of allergic pulmonary inflammation: prophylactic and therapeutic effect of an anti-IL-5 antibody.
Interleukin-5 (IL-5) is important in the control of differentiation, migration, and activation of eosinophils. In order to study the role of IL-5 in the development of eosinophilic inflammation of the airways, we have used a monoclonal antibody to murine IL-5 (TRFK-5) in a murine model of allergic pulmonary inflammation. B6D2F1 mice were sensitized with alum-precipitated ovalbumin and were challenged with aerosolized ovalbumin on day 12 after sensitization. Samples of bronchoalveolar lavage (BAL) fluid, lung tissue, blood, and bone marrow aspirate were collected at different times after ovalbumin challenge. Twenty-four hours after challenge there were significant increases in the number of eosinophils in the BAL fluid, lung tissue, and blood while bone marrow eosinophils were decreased. Treatment of sensitized mice with TRFK-5 (0.01-1 mg/kg, i.p.) 2 h before ovalbumin challenge reduced the numbers of eosinophils in the BAL fluid and lung tissue and prevented the decrease in bone marrow eosinophils in a dose-dependent fashion. The number of eosinophils in the BAL fluid, peribronchial and alveolar regions of the lung was also reduced when TRFK-5 (2 mg/kg, i.p.) was given up to 5 d after ovalbumin challenge. Furthermore, there was no evidence of increased epithelial damage, edema, or the presence of mucus that could have resulted from eosinophil apoptosis and release of toxic proteins after neutralization of IL-5. These results demonstrate an important role for IL-5 in the development of eosinophilic inflammation of the airways and for the migration of eosinophils from the bone marrow into blood in response to antigen challenge.(ABSTRACT TRUNCATED AT 250 WORDS)
Kung
T T
TT
Schering-Plough Research Institute, Kenilworth, NJ 07033-0539, USA.
Stelts
D M
DM
Zurcher
J A
JA
Adams
G K
GK
Egan
R W
RW
Kreutner
W
W
Watnick
A S
AS
Jones
H
H
Chapman
R W
RW
D000418:Albumins / Q000008:administration & dosage / Q000276:immunology; D000818:Animals; D000906:Antibodies / Q000627:therapeutic use; D004195:Disease Models, Animal; D006967:Hypersensitivity / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control; D007249:Inflammation / Q000276:immunology / Q000378:metabolism* / Q000517:prevention & control; D015848:Interleukin-5 / Q000032:analysis* / Q000276:immunology; D008171:Lung Diseases / Q000209:etiology / Q000276:immunology / Q000378:metabolism* / Q000628:therapy; D051379:Mice
D000418:Albumins; D000906:Antibodies; D015848:Interleukin-5