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

Am J Respir Crit Care Med. 2000 Oct;162(4 Pt 1):1377-82. doi: 10.1164/ajrccm.162.4.9911117.

Abstract

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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Allergens* / immunology
  • Asthma / drug therapy*
  • Asthma / immunology
  • Bronchi / drug effects
  • Bronchi / immunology
  • Bronchoalveolar Lavage Fluid / immunology
  • Bronchoscopy
  • Chemokine CCL11
  • Chemokines, CC*
  • Cyclosporine / administration & dosage*
  • Cyclosporine / adverse effects
  • Cytokines / metabolism*
  • Double-Blind Method
  • Eosinophils / drug effects*
  • Eosinophils / immunology
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism*
  • Humans
  • Interleukin-5 / metabolism*
  • Male
  • Middle Aged
  • Rhinitis, Allergic, Perennial / drug therapy*
  • Rhinitis, Allergic, Perennial / immunology
  • Rhinitis, Allergic, Seasonal / drug therapy*
  • Rhinitis, Allergic, Seasonal / immunology

Substances

  • Allergens
  • CCL11 protein, human
  • Chemokine CCL11
  • Chemokines, CC
  • Cytokines
  • Interleukin-5
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Cyclosporine