Effects of C-reactive Protein and Homocysteine on Cytokine Production: Modulation by Pravastatin.
Effects of C-reactive Protein and Homocysteine on Cytokine Production: Modulation by Pravastatin.
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DOI：
10.1111/j.1753-5174.2007.00003.x
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发表时间：
2008-07-01
期刊：
影响因子：
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通讯作者：
Stein, C Michael
中科院分区：
文献类型：
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作者：
Asanuma, Yu;Oeser, Annette;Stein, C Michael
目的：C反应蛋白(CRP)和同型半胱氨酸是心血管危险的标志物，可能具有炎症效应。HMG辅酶A还原酶抑制剂(他汀类)在体外具有抗炎作用，但尚不清楚体内这种反应是否继发于降脂。我们检验了一种假设，即CRP和同型半胱氨酸会刺激人全血中细胞因子的释放，而他汀类药物的短期治疗会抑制细胞因子的释放。方法：在37℃、5%CO(2)气氛下，用生理盐水、1微克/毫升脂多糖、50和100微克/L同型半胱氨酸、5微克/毫升重组人C反应蛋白孵育全血24小时，测定产生IL-6和单核细胞趋化蛋白-1的时间进程。15名健康志愿者每日服用普伐他汀40 mg，连续服药2天，测定服药前后血细胞因子反应。结果：重组人C反应蛋白和内毒素均可使全血中IL-6和单核细胞趋化蛋白-1的产生增加4倍以上(P<；0.001)，而同型半胱氨酸无明显作用。每天口服普伐他汀40 mg，连续2天，6h后CRP刺激的IL-6产生减少约20%(P=0.02)，但对MCP-1的产生无影响(P=0.69)。普伐他汀治疗对内毒素刺激的单核细胞趋化蛋白-1无影响，但可使IL-6轻度升高。结论：CRP可刺激人全血中动脉粥样硬化介质MCP-1和IL-6的产生，而同型半胱氨酸则无此作用。短期普伐他汀治疗可适度减弱CRP刺激的IL-6的产生，但不能抑制MCP-1的产生。
OBJECTIVE: C-reactive protein (CRP) and homocysteine are markers of cardiovascular risk that may have inflammatory effects. HMG coenzyme A reductase inhibitors (statins) have anti-inflammatory effects in vitro, but it is not clear if such responses in vivo are secondary to lipid lowering. We examined the hypothesis that CRP and homocysteine would stimulate cytokine release in human whole blood and that short-term treatment with a statin would inhibit it. METHODS: The time course of IL-6 and MCP-1 production was determined in whole blood incubated with saline, 1 microg/mL lipopolysaccaride (LPS), 50 and 100 microM/L DL-homocysteine, and 5 microg/mL human recombinant CRP for 24 hours at 37 degrees C under 5% CO(2) atmosphere. Cytokine responses were determined in blood drawn from 15 healthy volunteers before and after administration of pravastatin 40 mg daily for 2 days. RESULTS: Both human recombinant CRP and LPS significantly increased the production of IL-6 and MCP-1 in whole blood samples more than 4-fold (P < 0.001) but homocysteine did not. Oral administration of pravastatin, 40mg daily for 2 days, decreased CRP-stimulated IL-6 production by approximately 20% (P = 0.02) 6 hours after incubation, but did not affect MCP-1 production (P = 0.69). Pravastatin treatment did not affect LPS-stimulated MCP-1 but increased IL-6 modestly. CONCLUSIONS: CRP stimulated the production of the proatherogenic mediators MCP-1 and IL-6 in human whole blood, but homocysteine did not. CRP-stimulated production of IL-6, but not MCP-1, was modestly attenuated by short-term treatment with pravastatin.