Theophylline—an Immunomodulatory Role in Asthma?

Abstract

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)

The effect of a novel orally active selective PDE4 isoenzyme inhibitor (CDP840) on allergen-induced responses in asthmatic subjects

“…As the LAR is accompanied by inflammatory cell recruitment and often by an associated increase in BHR, it is considered to be a useful model of airway inflammation [39]. Corticosteroids, sodium cromoglycate, nedocromil sodium, theophylline and leukotriene antagonists are all successful in attenuating the LAR and the accompanying BHR [6,[39][40][41]. Treatment with theophylline, as well as attenuating the LAR, is associated with a decrease in activated eosinophils in bronchial biopsies 24 h after allergen exposure [8].…”

“…In recent years, it has become increasingly clear that, in addition to its action as a bronchodilator, theophylline has important immunomodulatory and anti-inflammatory actions [4]. In man, theophylline inhibits the allergeninduced late asthmatic response (LAR) and associated hyperresponsiveness [5,6]. Six weeks of treatment with theophylline has been shown to reduce the number of activated eosinophils recruited to the airway following allergen challenge, and decrease the numbers of activated CD4+ cells in bronchoalveolar lavage (BAL) fluid postchallenge [7,8].…”

Differential effect of phosphodiesterase 4 inhibitors on the proliferation of human peripheral blood mononuclear cells from normals and subjects with atopic dermatitis

“…It would therefore also seem plausible that the type 4 PDE inhibitors could be having a stimulatory effect on T suppressor cells. This is of interest given that theophylline has recently been suggested to possess immunomodulatory activity in asthmatic subjects (Ward et al, 1993;Jaffar et al, 1994).…”

Comparison of Single- And Multi-Stage Extrusion Versus Press-Coating Technique in Formulation of Modified-Release Tablets With Theophylline

“…Theophylline is also shown to reduce the need for oral prednisolone to relieve exacerbations that are not only controlled by bronchodilators in asthmatics. [12][13][14][15][16] One approach to increase the effectiveness of pharmacotherapy is to administer drugs while they are most effective and/or best tolerated. The principles of chronotherapy can be realized by choosing the right time for conventional tablets and capsules, or designing and characterizing drug delivery systems to synchronize drug release to the rate of disease activity.…”