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Immunological Investigations
A Journal of Molecular and Cellular Immunology
Volume 32, 2003 - Issue 1-2
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Original

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

, , , , & , M.D., Ph.D.
Pages 43-58 | Published online: 17 Mar 2003
 

Abstract

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.

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