Low-dose theophylline modulates T-lymphocyte activation in allergen-challenged asthmatics.
Theophylline has been shown by several investigators to attenuate the late asthmatic response (LAR) to inhaled allergen, suggesting that it has anti-inflammatory or immunomodulatory properties. We have, therefore, undertaken a double-blind, placebo-controlled study to examine the effects of low-dose theophylline on bronchoalveolar lavage (BAL) and blood T-lymphocyte profile and activation in asthmatics following antigen challenge and the development of a LAR. Peripheral blood and BAL samples were obtained from 17 subjects with mild atopic asthma before and after 6 weeks of treatment with either oral theophylline or placebo. The mean serum theophylline concentration achieved was 6.6 micrograms.mL-1, which is below the currently accepted therapeutic range. Following theophylline therapy, there was a significant decrease in the number of BAL lymphocytes compared to placebo. On flow cytometric analysis of BAL cells, a significant loss of CD3+ T-lymphocytes, comprising both CD4+ and CD8+ subsets, was demonstrated. Moreover, there was a decrease in the number of BAL CD4+ T-cells expressing the activation marker very late activation antigen-1 (VLA-1), and an apparent reduction in human leucocyte antigen-DR (HLA-DR). Correspondingly, this was accompanied in the blood by an elevation in the proportion of activated CD4+ T-lymphocytes, in particular those expressing HLA-DR. These findings provide further evidence that theophylline has an anti-inflammatory action in asthma.
Jaffar
Z H
ZH
Dept of Thoracic Medicine, King's College Hospital, London, UK.
Sullivan
P
P
Page
C
C
Costello
J
J
D000328:Adult; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology*; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001999:Bronchoscopy; D016516:CD4-CD8 Ratio; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D010366:Peak Expiratory Flow Rate / Q000187:drug effects; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D013806:Theophylline / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
D001993:Bronchodilator Agents; D013806:Theophylline