Attenuation of the allergen-induced late asthmatic reaction by cyclosporin A is associated with inhibition of bronchial eosinophils, interleukin-5, granulocyte macrophage colony-stimulating factor, and eotaxin.
The allergen-induced late asthmatic reaction (LAR) is associated with increases in bronchial eosinophils and basophils as well as upregulation of several eosinophil active cytokines and C-C chemokines. Cyclosporin A (CsA) was previously shown to inhibit the LAR, but not the early asthmatic reaction (EAR), and this was associated with a decrease in blood eosinophils. For these reasons, we determined whether CsA inhibited the allergen-induced increases in bronchial eosinophils, basophils, eotaxin, interleukin-5 (IL-5), and granulocyte macrophage colony-stimulating factor (GM-CSF). Subjects with a demonstrable LAR underwent bronchoscopy with biopsy and bronchoalveolar lavage (BAL) at baseline and then were randomly allocated to receive either CsA (n = 13) or placebo (n = 11) before challenge. A second bronchoscopy was performed 24 h later. The LAR, but not the EAR, was significantly attenuated in the CsA group compared with placebo (p < 0.05). CsA significantly inhibited the allergen-induced increases in IL-5 (p = 0.02) and GM-CSF (p = 0. 0028) in mRNA+ cells in BAL, and in a mAB against human activated eosinophils (EG2+) (p = 0.0227). We conclude that inhibition of the LAR by CsA may be related to its inhibitory effects on eosinophil-associated cytokines and chemokines. The beneficial effect of CsA in asthma may also be the result of inhibition of eosinophil accumulation.
Khan
L N
LN
Allergy and Clinical Immunology, Imperial College School of Medicine, National Heart and Lung Institute, London, United Kingdom.
Kon
O M
OM
Macfarlane
A J
AJ
Meng
Q
Q
Ying
S
S
Barnes
N C
NC
Kay
A B
AB
D000293:Adolescent; D000328:Adult; D000485:Allergens / Q000276:immunology; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology; D001980:Bronchi / Q000187:drug effects / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D001999:Bronchoscopy; D054413:Chemokine CCL11; D019742:Chemokines, CC; D016572:Cyclosporine / Q000008:administration & dosage* / Q000009:adverse effects; D016207:Cytokines / Q000378:metabolism*; D004311:Double-Blind Method; D004804:Eosinophils / Q000187:drug effects* / Q000276:immunology; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D006801:Humans; D015848:Interleukin-5 / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012221:Rhinitis, Allergic, Perennial / Q000188:drug therapy* / Q000276:immunology; D006255:Rhinitis, Allergic, Seasonal / Q000188:drug therapy* / Q000276:immunology
D000485:Allergens; C515456:CCL11 protein, human; D054413:Chemokine CCL11; D019742:Chemokines, CC; D016207:Cytokines; D015848:Interleukin-5; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D016572:Cyclosporine