Thrombin enhances the release of IL-6 by human monocytes through a differentiation-linked mechanism

In addition to its procoagulant activity, thrombin is mitogenic for a variety of cell types. It also activates a number of inflammatory cells including T lymphocytes, Natural Killer cells and is chemotactic for monocytes. To further understand the complex physiological functions of thrombin on monocytes. we investigated whether thrombin-induced activation was related to the level of monocyte differentiation. Using highly purified human -thrombin and the monocytic cell line U937, we investigated whether thrombin, has any effect on Interleukin-6 (IL-6) production and/or proliferation of U937 cells, differ entiated or not with Interferon- (IFN). At physiological concentrations (1-10 μg/ml, 30-300nM), thrombin enhanced the proliferation of IFN-differentiated U937 cells, while undiffereritiated U937 cells did not significantly respond. Enhanced proliferation was associated with increased IL-6 production in IFN-differentiated U937 cells (100% increase), while undifferentiated U937 cells did not produce any IL-6.Further, thrombin enhances the release of IL-6 by human peripheral blood monocytes. In addition, IFN-differentialed U937 cells bound thrombin with high affinity versus undifferentiated U937 cells. Together, these results suggest that thrombin enhances IL-6 production and proliferation in human monocytes through a differentiation-linked mechanism. This may be important for thrombin regulating the inflammatory response and the wound healing process, in which monocytes play an important role.