Carvedilol differentially regulates cytokine production from activated human peripheral blood mononuclear cells.
Chronic inflammation is one of the important mechanisms involved in atherosclerosis formation. The activated monocytes and their secreted cytokines contribute significantly to this inflammatory process. Here we examined the effects of carvedilol, a recently introduced cardio-protective alpha-1- and beta-receptor blocker, on cytokine production from various stimuli-activated human immune effector cells. By ELISA analysis, we showed that carvedilol inhibited interferon-gamma (IFN-gamma), but enhanced interleukin (IL)-12 production in phytohemagglutinin (PHA)- and concanavalin A (ConA)-stimulated human peripheral blood mononuclear cells (PBMCs). The production of tumor necrosis factor-alpha (TNF-alpha) was marginally affected. When purified monocytes were examined, we observed the consistent up-regulation of IL-12 production while both IL-10 and TNF-alpha were unaffected or marginally down-regulated, respectively, by carvedilol. In agreement with the observation in monocytes, the production of IL-12 from activated macrophages was also up-regulated by carvedilol. We concluded that carvedilol might mediate its therapeutic effects through differentially regulating cytokine production from activated mononuclear cells, including at least monocytes and macrophages.
Yang
Shih-Ping
SP
Cardiology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China.
Ho
Ling-Jun
LJ
Cheng
Shu-Meng
SM
Hsu
Yu-Lin
YL
Tsao
Tien-Ping
TP
Chang
Deh-Ming
DM
Lai
Jenn-Haung
JH
D000959:Antihypertensive Agents / Q000494:pharmacology; D002227:Carbazoles / Q000494:pharmacology*; D000077261:Carvedilol; D002478:Cells, Cultured; D002681:China; D003208:Concanavalin A / Q000494:pharmacology; D005544:Forecasting; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018664:Interleukin-12 / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D010835:Phytohemagglutinins / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D000959:Antihypertensive Agents; D002227:Carbazoles; D008070:Lipopolysaccharides; D010835:Phytohemagglutinins; D011412:Propanolamines; D014409:Tumor Necrosis Factor-alpha; D014665:Vasodilator Agents; D000077261:Carvedilol; D003208:Concanavalin A; D018664:Interleukin-12; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor