BACKGROUND: Several lines of evidence indicate that specific immunotherapy may act by modifying the patterns of cytokines produced by helper T cells. However, different protocols have been used and different results obtained. OBJECTIVES: To quantify the effect of specific immunotherapy on the TH1/TH2 T-cell cytokine pattern at the single cell level. METHODS: We examined the interferon-gamma/interleukin-4 ratio in peripheral blood CD4+ and CD8+ T cells from 12 subjects with house dust mite-sensitive asthma using a flow cytometric method of intracellular cytokine detection. Cytokine production was determined following stimulation with phorbol myristate acetate/ionomycin, a policlonal activator. Subjects were examined at three occasions: before specific immunotherapy, after the 3-months dose increase phase and after 1 year of treatment. During the treatment year patients kept a diary in which they recorded: (a) symptoms of asthma according to a 0-3 grading (0 = absent, 1 = mild, 2 = moderate, 3 = severe); (b) number of puffs (100 microg) per day of salbutamol required to control symptoms; and (c) peak expiratory flow. RESULTS: Specific immunotherapy improved clinical indices of disease activity including symptom scores and medication use during the treatment year, and had a marked effect in increasing the interferon-gamma/interleukin-4 ratio in peripheral blood CD4+ T cells already after the dose increase phase (5.47 +/- 1.5 vs 4.07 +/- 1.49\%, P = 0.03) with and a further rise after 1 year's treatment (16.12 +/- 2.8 vs 4.07 +/- 1.49 and 16.12 +/- 2.8 vs 5.47 +/- 1.5\%, P = 0.001 and P = 0.002, respectively). There were no significant changes in the interferon-gamma/interleukin-4 ratio in peripheral blood CD8+ T cells at the three times of the study. CONCLUSIONS: These data add to view that the efficacy of specific immunotherapy may be attributed to a modified cytokine secretion of CD4+ T cells.
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