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 microM 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 microM. However, at concentrations higher than 10 microM, 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 microM 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.
Division of Cardiology, Department of Internal Medicine, Tri-Service General Hospital, Taipei, Taiwan, ROC.
Shu-Meng
SM
Cheng
Shih-Ping
SP
Yang
Ling-Jun
LJ
Ho
Tien-Ping
TP
Tsao
Deh-Ming
DM
Chang
Jenn-Haung
JH
Lai
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002227:Carbazoles / Q000494:pharmacology*; D000077261:Carvedilol; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007249:Inflammation / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis*; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D011412:Propanolamines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D020298:U937 Cells
D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D012333:RNA, Messenger; D000077261:Carvedilol; D016753:Interleukin-10; D016178:Granulocyte-Macrophage Colony-Stimulating Factor