Abstract

Cytokine interactions in health & disease are very complex. There are conflicting reports on the cytokine IL-18 and its role in Th1 versus Th2 shift. The hypothesis that STAT-6 is expressed in monocyte/macrophages and that cytokine IL-18 has an effect on the phosphorylation of STAT-6 is addressed. Monocyte/macrophages were isolated by negative selection. The data indicates that the optimum concentration of IL-18 required for stimulation is 10μg/1x106 cells and 72 hour culture period is the optimum time for the induction of maximum levels of STAT-6 phosphorylation. We also observed total tyrosine phosphorylation of several intracellular proteins. Based on these studies, we propose that macrophages respond to IL-18 via STAT-6 phosphorylation and that IL-18 induces mitotic activity in monocyte/macrophages. Our data suggest that IL-18 actsin a more subtle manner as a costimulatory factor in the activation of STAT-6 in monocytes and provides evidence for a new immunoregulatoryeffect of the proinflammatory cytokine IL-18 on monocytes.

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

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