Two types of murine T-cell clones (TH1 and TH2) have been defined by studies of the cytokines they produce. In mice, TH1 cells are associated with classic delayed-type hypersensitivity (DTH), whereas TH2 cells appear to induce allergic inflammation. The IL-4 produced by TH2 clones and IFN-y derived from TH1 clones reciprocally regulate IgE synthesis in vitro.u Although helper T cells in humans cannot be classified as clearly as those in mice, there is some indirect evidence for the possibility of imbalance between IL-4 and IFN-y in humans. T-cell clones specific to Dp in allergic patients produce larger amounts of IL-4 than IFN-y, and in nonatopic patients these clones produce more IFN-y than IL-4.
The asthmatic group with positive specific IgE and allergic skin reaction to Dp had high serum IL-4 and total IgE, supporting the current hypothesis that TH2 clone dominantly responds to Dp in atopic individuals and easily releases large amounts of IgE antibody. mycanadianpharmacy.com
However, it is difficult to explain why IL-4 in asthmatics without atopic status significantly increased beyond that in control subjects (not so markedly as that in atopic asthmatics). In regard to this increase, it is considered that specific IgE against an unknown antigen other than house dust mite may be involved in nonatopic asthma or IL-4 may be secondarily produced by TH2 cells associated with production of IL-5, which is a cytokine essential to eosinophil infiltration to bronchial mucosa regarded as the fundamental pathologic sign of bronchial asthma.
In this study, total IgE did not correlate with IL-4 in asthmatics, the reason for which is also uncertain. Individual differences of participation of IFN-y which has a competitive effect on the action of IL-4 and of IL-5 or IL-6 which is essential to induce В cells into plasma cells have not been clarified. Also, there may be large individual differences in types of nonspecific IgE-producing clones, of which production may be equally enhanced by IL-4, but clinical significance is unclear. These may be some of the reasons for the lack of correlation.
Serum sFceRII did not increase more in atopic than in nonatopic asthmatics and did not show a relationship to IL-4 or total IgE. To date and to our knowledge, the only agent capable of inducing FceRII expression on В cells is IL-41213 and its suppressor is IFN-y. SFceRII is first released as a 37- to 33-kDa molecule and subsequently transformed into a stable 25-kDa fragment. Unstable 37- to 33-kDa molecules have a potent effect on the synthesis of IgE, and 25-kDa molecules bind to IgE to neutralize or downregulate IgE-mediated immune response. SFceRII consists of multiple components with different functions for IgE regulation. However, it remains uncertain at present how sFceRII, with conflicting possibilities for IgE production, takes part in IgE regulation or how it is dependent on IL-4 in vivo. The study of other cytokines, particularly IFN-y, is necessary to clarify the participation of IL-4 and sFceRII in the regulation mechanism of IgE synthesis.
In conclusion, these three markers in the asthmatic patients elevated compared with the control subjects, which indicates that T- and В-cell activation is present in asthmatics. High IL-4 in atopic asthmatics suggests the preferential activation of TH2 cells. Total IgE was unrelated to IL-4 or sFceRII. The regulatory mechanism of IgE synthesis would not appear to be the only responsible factor.