IL-1 and TNF antagonists prevent inhibition of fracture healing by ethanol in rats

IL-1 and TNF antagonists prevent inhibition of fracture healing by ethanol in rats
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DOI:
10.1093/toxsci/kfi002
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发表时间:
2004-12-01
影响因子:
3.8
通讯作者:
Lumpkin, CK
Lumpkin, CK
中科院分区:
医学2区
文献类型:
--
作者:
Perrien, DS;Wahl, EC;Lumpkin, CK

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我们检验了联合应用IL-1和TNF拮抗剂可保护骨折愈合免受慢性乙醇暴露抑制的假设。在建立外固定胫骨骨折之前和之后三周,通过胃内输注给成年雄性大鼠喂食流质饮食+/-乙醇(CON和ETOH)。从骨折当天开始,每个饮食组的一半接受2.0 mg/kg/天IL-1 ra和2.0 mg/kg/2天sTNFR 1(CON + ANTAG和ETOH + ANTAG),而所有其他动物仅接受溶媒(CON + VEH和ETOH + VEH)。离体X线片评分和pQCT分析显示,与所有其他组相比,ETOH + VEH组的桥接发生率显著降低,总矿物质含量降低。这些结果首次支持了IL-1和TNF拮抗剂能够保护骨折愈合免受与慢性乙醇消耗相关的抑制的假设。
We tested the hypothesis that combined administration of IL-1 and TNF antagonists would protect fracture healing from inhibition by chronic ethanol exposure. Adult male rats were fed a liquid diet +/- ethanol (CON and ETOH) by intragastric infusion for three weeks prior to and three weeks after creation of an externally fixated tibial fracture. Beginning the day of fracture, one-half of each dietary group received 2.0 mg/kg/day IL-1ra and 2.0 mg/kg/2-days sTNFR1 (CON + ANTAG and ETOH + ANTAG), while all other animals received vehicle alone (CON + VEH and ETOH + VEH). Scoring of ex vivo radiographs and analysis by pQCT revealed a significantly lower incidence of bridging and reduced total mineral content in the ETOH + VEH group compared to all other groups. These results support, for the first time, the hypothesis that IL-1 and TNF antagonists are capable of protecting fracture healing from the inhibition associated with chronic ethanol consumption.