Cyclosporin A, apoptosis of BAL T-cells and expression of Bcl-2 in asthmatics

Eur Respir J. 2003 Aug;22(2):207-12. doi: 10.1183/09031936.03.00098902.

Abstract

The late asthmatic reaction is characterised by elevated numbers of interleukin-4/interleukin-5/CD4-positive T-helper cells type 2 in bronchoalveolar lavage fluid (BALF). Cyclosporin A (CsA) is known to inhibit T-cell proliferation, induce apoptosis of CD4-positive T-cells and downregulate cytokine gene expression. It was assessed whether CsA-induced inhibition of the late asthmatic reaction was associated with apoptosis of BALF T-lymphocytes and other cell types, as well as expression of the antiapoptotic protein B-cell leukaemia/lymphoma 2 gene product (Bcl-2). BALF cells were obtained from asthmatics at baseline and 24 h after allergen-inhalation challenge following prior administration of CsA (n=13) or placebo (n=11). The number of apoptotic CD3-positive T-lymphocytes increased in the CsA but not the placebo group. The numbers of Bcl-2-positive cells were significantly reduced in the CsA but not the placebo group. The majority of Bcl-2-positive cells were CD3-positive T-lymphocytes. The beneficial effect of cyclosporin A in asthma may be related to its inhibitory effect on the late asthmatic reaction via induction of T-cell apoptosis and decreased B-cell leukaemia/lymphoma 2 gene product levels.

Publication types

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

MeSH terms

  • Apoptosis / drug effects*
  • Apoptosis / genetics
  • Asthma / genetics
  • Asthma / pathology*
  • Bronchial Provocation Tests
  • Bronchoalveolar Lavage Fluid / cytology
  • Cyclosporine / pharmacology*
  • Double-Blind Method
  • Gene Expression / drug effects
  • Gene Expression / genetics
  • Genes, bcl-2 / drug effects*
  • Genes, bcl-2 / genetics
  • Humans
  • Immunosuppressive Agents / pharmacology*
  • T-Lymphocytes / drug effects*
  • Time Factors

Substances

  • Immunosuppressive Agents
  • Cyclosporine