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Aim: To investigate the effect of theophylline on the naive T cell differentiation and the probable role of interleukin-12 (IL-12)., Methods: Naive cord blood T cells were treated with theophylline 10 mg/L for 3 d after stimulation with PHA 100 mg/L. Differentiation of T cells was analyzed by flow cytometry. Theophylline 10 mg/L and IL-12-mAb 0.025 mg/L were added in cord blood mononuclear cell (CBMC) cultures primed with LPS 1 mg/L to detect the levels of IL-12 and IL-12P40. The whole blood cultures were obtained from twelve health volunteers with or without administration of theophylline (200 mg). Cytokines were measured by enzyme linked immuno-sorbent assay., Results: Theophylline promoted T helper 1 (Th1) cells differentiation from naive T cells (21.9 %+/-10.3 % vs 9.4 %+/-5.6 %, P<0.05), but had no significant effect on Th2 deviation. But theophylline inhibited the production of IL-12 and IL-12P40 by CBMC in vitro (28+/-6 ng/L vs 57+/-14 ng/L and 88+/-34 ng/L vs 214+/-82 ng/L, P<0.01) and reduced IL-12 and IL-12P40 levels in whole blood cultures from healthy subjects (19+/-11 ng/L vs 31+/-15 ng/L and 92+/-13 ng/L vs 196+/-49 ng/L, P<0.01)., Conclusion: Theophylline promoted the differentiation of Th1 cells. IL-12 seemed not to be involved in this process.

Aim: To investigate the mechanism of anti-inflammatory action of theophylline on asthma., Methods: Nineteen asthmatic subjects were administered 200 mg sustained-release theophylline twice daily for 4 weeks. The number of CD4+ T lymphocytes, eosinophils, and the levels of interleukin (IL)-5 and interferon gamma (IFN-gamma) in sputum pre- and post-administration were measured by direct immunofluorescene technique, Wright's stain and enzyme-linked immunosorbent assay, respectively. The symptom scores and lung function were also evaluated., Results: Theophylline treatment significantly improved symptom scores and FEV1.0, FEV1.0 % (P < 0.05) and reduced sputum eosinophils (P < 0.01) in asthmatic subjects. These were accompanied by a decrease in sputum IL-5 level (P < 0.01), but sputum CD4+ T lymphocytes and IFN-gamma had no significant change (P >0.05). The mean (range) serum theophylline concentration in final steady state was 7.9 (3.9 - 12.9) mg/L., Conclusion: The anti-inflammatory action of theophylline in asthma may result from reduction of IL-5 production in the airways.