Carvedilol Modulates In-Vitro Granulocyte-Macrophage Colony-Stimulating Factor-Induced Interleukin-10 Production in U937 Cells and Human Monocytes.

Both granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-10 (IL-10) are important mediators regulating inflammatory responses. Inflammatory processes have an important role in atherogenesis. In this paper, the effects of carvedilol on GM-CSF-induced IL-10 production were examined on human monocytic cell line, U937, and purified human monocytes. First, we showed that one-time carvedilol pretreatment at concentrations 0.3-10 μM dose-dependently inhibited GM-CSF-induced IL-10 production in U937 cells. In addition, we found carvedilol to be non-cytotoxic at concentrations equal to or less than 10 μM. However, at concentrations higher than 10 μM, carvedilol induced programmed cell death in U937 cells. The inhibition of GM-CSF-induced IL-10 production by carvedilol was also observed at the expression of mRNA. Furthermore, the inhibition of IL-10 production was demonstrated in GM-CSF-activated purified human peripheral blood monocytes. Finally, long-term carvedilol pretreatment of U937 cells up to 2 months at concentrations of 1.0 μM mildly enhanced the IL-10 production. Our observations that carvedilol modulated GM-CSF-induced IL-10 production may have some implication in understanding the broad-spectrum effects of carvedilol in regulating inflammatory reactions. [ABSTRACT FROM AUTHOR]