Abstract

STAT-6 is a central mediator of IL-4-induced gene responses. It has been shown that STAT-6 is expressed in B cells and T cells upon stimulation with IL-4. Interleukin-12 (IL-12) and IL-18 are the key factors for the induction of Th1 Cells, early signals being involved in Th2 differentiation if any by IL-18 are less well characterized. We have investigatedthe mechanisms employed by IL-18 and IL-4 to control expression of STATs. Since we have shown in earlier studies that Th2 cytokines protect cells from apoptosis, we explored the possible role of the controversial cytokine IL-18 on Th2 shift and analyzed the effects of IL-18 on CD4+ T cells. Cells were cultured either with IL-18, IL-4, IL-18 + CD28 for different time points. The optimum time required for the phosphorylation of STAT-6 when stimulated with IL-18 was 72 hours. This effect of STAT-6 phosphorylation was blocked by addition of anti-IL-18 antibody in the culture. However, phosphorylation of STAT-1 and STAT-4 was seen by 24 hours. Furthermore, when cells were stimulated with anti-CD28 antibody plus IL-18, there is accelerated and enhanced phosphorylation of STAT-6. These studies may suggest that IL-18 serves as a negative feed back mechanism on inflammatory responses.

Grant from C.W.Post Campus Research Committee of Long Island University, New York supported this work.

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