Kinetics of the development and recovery of the lung from IgE-mediated inflammation: dissociation of pulmonary eosinophilia, lung injury, and eosinophil-active cytokines.
Events occurring up to 16 d after antigen challenge were characterized using a novel protocol employing four bronchoscopies, two segmental antigen challenge (SAC) procedures (on Days 1 and 2), and six bronchoalveolar lavages (BALs) (on Days 1, 2, 9, and 16) in three groups: ragweed allergic asthmatics with dual phase airway reactions (AA-D), allergic asthmatics with a single early airway reaction (AA-S), and nonallergic nonasthmatic control subjects. In AA-D subjects, SAC produced a marked eosinophilic inflammatory response at 24 h associated with eosinophil degranulation (eosinophil cationic protein [ECP] in BAL fluid) and lung injury, which largely resolved by Day 16. When the second antigen-challenged segment (SAC performed on Day 2) was lavaged 7 d after challenge (Day 9), a persistent pulmonary eosinophilia was noted accompanied by minimal elevations in ECP and albumin. Eosinophil-active cytokines showed unique patterns: interleukin-5 (IL-5) increased in the antigen segment on Day 2 then returned to baseline after 7 d; granulocyte-macrophage colony-stimulating factor (GM-CSF) peaked at Day 2 but was persistently elevated throughout Day 16 in antigen segments, and increased in control segments at late time points; IL-3 levels were constant and similar in antigen and control segments. Changes were specific to AA-D subjects in comparison with control subjects. Elements of the IgE-mediated pulmonary inflammatory response differ markedly in their development and resolution.
Shaver
J R
JR
Department of Medicine, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania 19107-5083, USA.
Zangrilli
J G
JG
Cho
S K
SK
Cirelli
R A
RA
Pollice
M
M
Hastie
A T
AT
Fish
J E
JE
Peters
S P
SP
D000328:Adult; D000485:Allergens / Q000009:adverse effects*; D000941:Antigens; D001249:Asthma / Q000175:diagnosis*; D001798:Blood Proteins / Q000032:analysis; D001985:Bronchial Provocation Tests; D018893:Bronchoalveolar Lavage; D001999:Bronchoscopy; D047091:Eosinophil Granule Proteins; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000009:adverse effects*; D018836:Inflammation Mediators / Q000032:analysis; D007700:Kinetics; D008297:Male; D011657:Pulmonary Eosinophilia / Q000209:etiology / Q000503:physiopathology*; D012129:Respiratory Function Tests; D012260:Ribonucleases
D000485:Allergens; D000941:Antigens; D001798:Blood Proteins; D047091:Eosinophil Granule Proteins; D018836:Inflammation Mediators; D007073:Immunoglobulin E; D012260:Ribonucleases