Bronchopulmonary hyperreactivity and lung eosinophil sequestration but not their migration to the alveolar compartment are independent of interleukin-5 in allergic mice.
IL-5 is present in the lung and in the circulation following allergenic challenges in humans and in animals, but its role in bronchopulmonary hyperreactivity (BHR) and lung and bronchoalveolar lavage fluid (BALF) eosinophilia remains unclear. Because compartmentalization of IL-5 is recognized, the anti-IL-5 monoclonal antibody TRFK-5 or its isotype control GL113 were delivered selectively intranasally (i.n.) and/or intravenously (i.v.) before the prior i.n. challenge with 10 mug OVA in BALB/c and BP2 "Biozzi" mice immunized according to optimized protocols with read-outs taken 24 h later. IL-5 in the BALF was suppressed by i.n. TRFK-5, whereas its production persisted in the serum. Conversely, i.v. TRFK-5 suppressed IL-5 in the serum but not in the BALF. IL-5 was suppressed in conditioned medium from lung explants from mice treated with i.n. TRFK-5, which did not affect the other Th2 cytokines, IL-4 and IL-13. IL-5 is thus present in the alveolar, pulmonary and circulatory compartments following an i.n. allergenic challenge. When specific anti-IL-5 antibodies were delivered by the same i.n. route, BALF eosinophilia was markedly reduced, whereas BHR and lung eosinophil sequestration persisted totally or mostly, in both strains. The passage of eosinophils from lungs to alveoli depends on IL-5 released into the BALF, but not into circulation, whereas their lung sequestration and BHR are mostly IL-5-independent. IL-5 alone does not account for the complexities of BHR or of eosinophil tissue trapping, and lung-targeted immunobiologicals should be delivered into the appropriate compartment in order to assess the role of specific mediators in experimental airways/lung allergy.
Proust
Barbara
B
Unité de Pharmacologie Cellulaire, Unité Associée Institut Pasteur-INSERM U.485, 25, rue du Docteur-Roux, 75724 Paris Cedex 15, France.
Ruffié
Claude
C
Lefort
Jean
J
Vargaftig
B Boris
BB
D000818:Animals; D016535:Bronchial Hyperreactivity / Q000503:physiopathology*; D001992:Bronchoalveolar Lavage Fluid; D002451:Cell Compartmentation; D002465:Cell Movement / Q000502:physiology*; D004804:Eosinophils / Q000166:cytology*; D006967:Hypersensitivity / Q000473:pathology / Q000503:physiopathology*; D015847:Interleukin-4 / Q000378:metabolism; D015848:Interleukin-5 / Q000502:physiology*; D008168:Lung / Q000166:cytology / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011650:Pulmonary Alveoli / Q000166:cytology*; D013045:Species Specificity
D015848:Interleukin-5; D015847:Interleukin-4