Evaluation of Th1/Th2 ratio and cytokine production profile during acute exacerbation and convalescence in asthmatic children

Background: Th2-type cytokines, such as IL-4 and IL-5, are generally believ ed to play an important role in the pathogenesis of allergic asthma. In con trast, Th1-type cytokine, especially interferon (IFN)-gamma, is thought to have a downregulatory effect on Th2 immune response cells. Thus, the imbala nce of Th1 and Th2 cells may be a key factor in relation to disease severit y. Objective: The aim of this study is to examine the changes in the Th1/Th2 r atios and cytokine production profiles of asthmatic children at acute attac ks and convalescent stages. Methods: Twelve asthmatic patients were included in this study. The percent ages of IFN-gamma- or IL-4-producing cells were determined with a flow-cyto metric method of intracellular protein detection. Fresh whole blood obtaine d from normal controls and patients at two stages was stimulated with brefe ldin A, phorbol myristate acetate, and ionomycin for 4 hours. Cells were fi xed and stained intracellularly with fluorescein isothiocyanate- or phycoer ythrin-conjugated antibody specific to each cytokine in combination with an ti-CD4. ELISA assays were applied to measure cytokine concentrations of sup ernatant from peripheral blood mononuclear cells (PBMC) activated with phor bol myristate acetate and ionomycin for 24 hours. Results: Among CD4(+) cells. the percentage of IL-4(+) cells decreased sign ificantly from 8.18 +/- 4.77% at acute attacks to 4.18 +/- 1.26% (P < .020) at convalescence. The percentage of IFN-<gamma>(+) cells also decreased fr om 13.49 +/- 4.21% to 9.03 +/- 5.42% (P < .052). The Th1/Th2 ratios of pati ents at the two stages were similar, and both were lower than the normal co ntrols. Significantly higher IL-5 and lower IFN-<gamma> production were det ected from activated PBMC of asthmatic patients than normal controls. Conclusions: The decrease of IFN-gamma (+) and IL-4(+) cells detected at th e single-cell level may explain the potential mechanism of convalescence fr om acute asthma attacks. High Th1/Th2 ratio and low IL-5 production from th e PBMC of normal controls support the idea of a biased Th2 immune response in asthmatic patients.