Childhood minimal minimal change nephrotic syndrome (MCNS) is often associated with hyper-sentivity reactions and considered to be caused by immune dysfunction.
The elevated serum IgE levels and atopic symptoms have been frequently observed in these patients. The present therapy for MCNS mainly depends on corticosteroid, alkylating agents such as cholrambucil, cyclophosphamide and recently developed new
immunosuppressive agent, cyclosporin A(Cy-A). However, frequent relapses and severe side effects caused by such therapy necessitiate development of a more specific and effective therapeutic regimen.
Recently, a T cell derive cytokine, interleukin 4(IL-4) is being recognized as a major cytokine upregulating IgE production and response, while interferon-γ(IFN-γ) counteracts IL-4 actions to downregulate the IL-4 induced IgE response. IIence,
the
present study is aimed to investigate the role of IL-4 in MCNS and potential effects of methylprednisolone (MP). Cy-A, or IFN-γon the IL-4 activities through the regulation of a IgE receptor (CD23) expression in MCNS.
Using freshly isolated peripheral blood from active MCNS patients and normal controls, it was found that not only serum IgE levels, but also membrane-bound IgE receptor expression and soluble IgE receptor production were also significantly higher
in
MCNS than in normal controls, which in turn correlated well with the increased IL-4 activities in the patient sera.
In in vitro cultures, IL-4 efficiently induced IgE receptor expression on MCNS B cell membrane in a dose dependent manner. Treatment with MP, Cy-A or IFN-γ all resulted in the inhibition of the IL-4 induced IgE receptor expression by these cells
in
both membrane bound and soluble forms. The degrees of inhibition was greater by MP or IFN-γthan Cy-A. Combination treatment studies revealed that a combined treatment with IFN-γ and MP was the most effective to result in a synergistic
inhibition
of
the IL-4 induced IgE receptor expression at both mRNA and protein levels. Interestingly among MCNS patients receiving a steroid therapy, those who responded with a clinical remission demonstrated a noticeable decrease in IgE receptor levels on
their B
cell. From these results it is concluded that MCNS is highly associated with not only increased serum IgE, but also elevated IL-4 activities and IgE receptor expression. In addition, combination therapy of MP & IFN-γ may be effective in the
control of
MCNS through the inhibition of IL-4 activities as manifest by down-regulation of the IgE receptor.
|