The late, but not early, asthmatic response is dependent on IL-5 and correlates with eosinophil infiltration.
Early-phase reactions (EPRs) and late-phase reactions (LPRs) are characteristic features of bronchial asthma, although the pathogenetic mechanisms responsible for each of the responses are not fully defined. A murine model of EPRs and LPRs was developed to investigate the role of IL-5 and eosinophils in development of both responses. After initial intraperitoneal sensitization and airway challenge to ovalbumin (OVA), mice were provoked by additional exposure to OVA. An EPR, characterized by a transient increase in airway responsiveness, was observed 5-30 minutes after antigen provocation. This response was followed by an LPR that reached its maximum at 6 hours after challenge and was characterized by increased airway responsiveness and significant lung eosinophilia. The EPR was blocked by cromoglycate and albuterol, whereas the LPR was abolished by cromoglycate and hydrocortisone. Before provocation with allergen, administration of anti-IL-5 antibody prevented the influx of eosinophils into the lung tissue and abolished the LPR but not EPR. These results suggest that IL-5 and eosinophils are essential for development of the LPR, but not EPR, in this model.
Cieslewicz
G
G
Division of Basic Sciences, Department of Pediatrics, Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado 80206, USA.
Tomkinson
A
A
Adler
A
A
Duez
C
C
Schwarze
J
J
Takeda
K
K
Larson
K A
KA
Lee
J J
JJ
Irvin
C G
CG
Gelfand
E W
EW
D000280:Administration, Inhalation; D000485:Allergens / Q000008:administration & dosage / Q000276:immunology; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D001249:Asthma / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D016535:Bronchial Hyperreactivity / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002465:Cell Movement / Q000276:immunology*; D004804:Eosinophils / Q000276:immunology / Q000473:pathology / Q000502:physiology*; D007114:Immunization; D015848:Interleukin-5 / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D007958:Leukocyte Count; D008168:Lung / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D013997:Time Factors
D000485:Allergens; D018927:Anti-Asthmatic Agents; D000911:Antibodies, Monoclonal; D015848:Interleukin-5; D010047:Ovalbumin