Cyclosporin A, apoptosis of BAL T-cells and expression of Bcl-2 in asthmatics.
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.
Ying
S
S
Dept of Allergy and Clinical Immunology, Faculty of Medicine, Imperial College London, National Heart & Lung Institute, London, UK.
Khan
L N
LN
Meng
Q
Q
Barnes
N C
NC
Kay
A B
AB
D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D001249:Asthma / Q000235:genetics / Q000473:pathology*; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016572:Cyclosporine / Q000494:pharmacology*; D004311:Double-Blind Method; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D019254:Genes, bcl-2 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects*; D013997:Time Factors
D007166:Immunosuppressive Agents; D016572:Cyclosporine