IL-5 is the predominant eosinophil-active cytokine in the antigen-induced pulmonary late-phase reaction.
The mechanism of airway eosinophilia during antigen-induced inflammation was investigated by measurement of eosinophil-active cytokines utilizing an eosinophil survival assay. In the first study, 4 patients with allergic rhinitis underwent segmental bronchoprovocation (SBP) with low, medium, and high doses of ragweed extract instilled into different bronchial subsegments; bronchoalveolar lavage (BAL) fluids were collected from each segment 12 min and 48 h after challenge. Eosinophil granule proteins and eosinophil survival activity were significantly elevated in the 48-h (late-phase) BAL fluids from these segments. Correlations were observed between the concentrations of eosinophil granule proteins and eosinophil survival activity (rs = 0.717 to 0.880, p < 0.001) in BAL fluids. Eosinophil survival activity was completely neutralized by anti-IL-5 monoclonal antibody in five of the seven 48-h samples tested representing three of the 4 patients. In the two remaining samples, eosinophil survival activity was only partially neutralized by either anti-IL-5 antibody or anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) but was completely neutralized by anti-IL-5 and anti-GM-CSF in combination. Subsequently, in the second study, 10 patients with allergic rhinitis were challenged by SBP with ragweed extract. Eosinophil survival activity was significantly elevated in the 48-h BAL fluids; this activity was partially neutralized by anti-IL-5 antibody about (48%) and completely neutralized by the combination of anti-IL-5 and anti-GM-CSF antibodies. These findings suggest that the eosinophil survival activity in the late inflammatory lesions following SBP with allergen is mainly associated with IL-5, with small contributions from GM-CSF.(ABSTRACT TRUNCATED AT 250 WORDS)
Ohnishi
T
T
Department of Immunology, Mayo Clinic, Rochester, MN 55905.
Kita
H
H
Weiler
D
D
Sur
S
S
Sedgwick
J B
JB
Calhoun
W J
WJ
Busse
W W
WW
Abrams
J S
JS
Gleich
G J
GJ
D000328:Adult; D000485:Allergens / Q000008:administration & dosage*; D001798:Blood Proteins / Q000032:analysis; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002470:Cell Survival; D047091:Eosinophil Granule Proteins; D047209:Eosinophil Peroxidase; D047208:Eosinophil-Derived Neurotoxin; D004804:Eosinophils / Q000502:physiology*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000502:physiology; D006801:Humans; D007377:Interleukin-3 / Q000502:physiology; D015848:Interleukin-5 / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009498:Neurotoxins / Q000032:analysis; D010544:Peroxidases / Q000032:analysis; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D012260:Ribonucleases
D000485:Allergens; D001798:Blood Proteins; D047091:Eosinophil Granule Proteins; D007377:Interleukin-3; D015848:Interleukin-5; D009498:Neurotoxins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D047209:Eosinophil Peroxidase; D010544:Peroxidases; D047208:Eosinophil-Derived Neurotoxin; D012260:Ribonucleases