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Am. J. Respir. Crit. Care Med., Volume 162, Number 4, October 2000, 1377-1382

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

L. NASREEN KHAN, ONN MIN KON, ALISON J. MACFARLANE, QIU MENG, SUN YING, NEIL C. BARNES, and A. BARRY KAY

Allergy and Clinical Immunology, Imperial College School of Medicine, National Heart and Lung Institute, London, United Kingdom; and London Chest Hospital, Bethnal Green, United Kingdom

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.




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