Theophylline--an immunomodulatory role in asthma?
Theophylline, a drug used for the treatment of asthma, is recognized as an immunomodulator affecting T-lymphocytes both in vitro and in vivo. The effect of slow-release theophylline (Uniphyllin Continus) on the late asthmatic response (LAR) has been compared with placebo before and after 5 wk of treatment in a double-blind, randomized, parallel group study. Nineteen volunteers with stable mild asthma successfully completed the study. All were dual responders with a documented late response to inhaled house dust mite extract. The LAR was assessed both in terms of changes in lung function and in peripheral blood T-lymphocyte subsets. The mean (SEM) maximal late fall in FEV1 before and after treatment was 28.8 (4.1)% and 7.8 (2.0)% with theophylline, versus 35.8 (5.1)% and 29.1 (5.0)% with placebo (p = 0.046; Cl, 0.3-26.9). Corresponding figures for specific airway conductance (SGaw) were 46.4 (8.4)% and 7.2 (8.0)% with theophylline versus 46.2 (7.2)% and 44.8 (7.7)% with placebo (p = 0.008; Cl, 11.2 to 64.1). This was achieved at a mean (SD) trough serum theophylline level of only 7.8 (3.5) micrograms/ml. Airway responsiveness to methacholine was not significantly changed 24 h after the initial allergen challenge. There was a trend towards a decrease in baseline responsiveness after treatment with theophylline compared with that after placebo (p = 0.07). Studies of peripheral blood lymphocytes showed a modifying effect of treatment on the allergen-induced changes in CD4 and CD8 counts 48 h after challenge. Previous studies have shown a protective effect of theophylline on the LAR at serum theophylline concentrations within the conventional range for bronchodilation.(ABSTRACT TRUNCATED AT 250 WORDS)
Ward
A J
AJ
Department of Thoracic Medicine, King's College School of Medicine and Dentistry, London, United Kingdom.
McKenniff
M
M
Evans
J M
JM
Page
C P
CP
Costello
J F
JF
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000485:Allergens; D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D001985:Bronchial Provocation Tests; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D004341:Drug Evaluation; D004391:Dust; D005541:Forced Expiratory Volume / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007958:Leukocyte Count / Q000187:drug effects; D008168:Lung / Q000187:drug effects / Q000503:physiopathology; D016210:Methacholine Chloride; D008875:Middle Aged; D008925:Mites / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D013806:Theophylline / Q000627:therapeutic use*
D000276:Adjuvants, Immunologic; D000485:Allergens; D003692:Delayed-Action Preparations; D004391:Dust; D016210:Methacholine Chloride; D013806:Theophylline