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

¹ Dept of Allergy and Clinical Immunology, Faculty of Medicine, Imperial College London, National Heart & Lung Institute, ² Division of Asthma, Allergy and Lung Biology, Guy's, King's and St Thomas' School of Medicine and ³ London Chest Hospital, London, UK

CORRESPONDENCE: A.B. Kay, Dept of Allergy and Clinical Immunology, Faculty of Medicine, Imperial College London, National Heart & Lung Institute, Dovehouse Street, London, SW3 6LY, UK. Fax: 44 20 73763138. E-mail: a.b.kay@ic.ac.uk

Keywords: apoptosis, asthma, bronchoalveolar lavage, cyclosporin A, cytokine

Received: October 29, 2002
Accepted February 20, 2003

This study was supported by the National Asthma Campaign, London, UK.

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.

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