Korean Journal of Nephrology 1992;11(1):10-22.

미세변화 신증후군의 발병기전에 있어서 IdE Receptor의 역할과 새로운 면역치료법의 개발에 관한 연구 ( 2 )

조병수 , 안창일 , 이충은 , 변광호

Abstract

Childhood minimal change nephrotic syndrome (MCNS) is often associated with hyper-sentivity reac- tions and considered to be caused by immune dysfunc- tion. The elevated serum IgE levels and atopic symptoms have been frequently observed in these patients. The present therapy for MCNS mainly depends on cor- ticosteroids, alkylating agents such as chlorambucil, cyclophosphamide and recently developed new im- munosuppressive 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 derived cytokine, interleukin 4 (IL-4) is being recognized as a major cytokine up- regulating IgE production and response, while interferon-y (IFN-y) counteracts IL-4 actions to down- regul yte the IL-4 induced IgE response. Hence, the present study is aimed to investigate the role of IL-4 in MCNS and potential effects of methylprednisolone (MP). Cy-A, or IFN-y on 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 in- creased IL-4 activities in the patient sera. In in vitro cultures, IL-4 efficiently induced IgE rece- ptor expression on MCNS B cell membrane in a dose- dependent manner. Treatment with MP, Cy-A or IFN- y 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-y than Cy-A. Combination treat- ment studies revealed that a combined treatment with IFN-y 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. Interest- ingly among MCNS patients receiving a steroid therapy, those who responded with a clinical remission demon- strated 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-y may be effective in the control of MCNS through the inhibition of IL-4 activities as manifest by down-regulation of the IgE receptor.