Interleukin-6 causes myocardial failure and skeletal muscle atrophy in rats
Interleukin-6 causes myocardial failure and skeletal muscle atrophy in rats
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DOI：
10.1161/01.cir.0000156469.96135.0d
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发表时间：
2005-03-01
期刊：
影响因子：
37.8
通讯作者：
Decramer, M
中科院分区：
文献类型：
--
作者：
Janssen, SPM;Gayan-Ramirez, G;Decramer, M
背景-白细胞介素(IL)-6对骨骼肌功能的影响仍然存在争议。方法和结果-研究了重组人IL-6皮下给药7天的效果，分别为50、100和250 μ g.kg（-1）。D(-1)，大鼠。骨骼肌质量呈剂量依赖性下降（随着剂量的增加：膈肌为-10%，P = NS; -15%, P = 0.0561; -15% P < 0.05；腓肠肌为-9%，P = NS; -9%, P = NS; -18%, P < 0.005），因为所有纤维类型的横截面面积减少，而膈肌的收缩特性没有改变。心血管变量显示出剂量依赖性心脏扩张（舒张末期容积：对照组，78 μ l；中等剂量，123 μ l；高剂量，137 μ l, P < 0.001），收缩压降低（对照组，113毫米汞柱；中等剂量，87毫米汞柱；高剂量，90毫米汞柱，P = 0.037），心肌收缩力降低（负荷前可恢复的卒中工作：对照组，79毫米汞柱；中等剂量，67毫米汞柱；高剂量，48毫米汞柱，P < 0.001）。肺水肿通过增加的干湿比（对照组，4.2；中等剂量，4.6；高剂量，4.5;P < 0.001）和显微镜检查结果证实。这些心血管改变导致器官血流减少，特别是横膈膜血流减少(对照组，0.56 mL.min(-1).g(-1)；中剂量，0.21 mL.min(-1).g(-1)；高剂量：0.23 mL.min(-1).g(-1)；P = 0.037)。体外重组人IL-6给药没有引起膈肌力或耐力的任何改变。结论-即使短期给药，IL-6也明显引起通气性和外周骨骼肌萎缩。IL-6引起的心肌衰竭导致的血流重新分配可能是导致肌肉萎缩的原因，因为IL-6对膈肌没有任何直接作用。
Background - The impact of interleukin (IL)-6 on skeletal muscle function remains the subject of controversy.Methods and Results - The effects of 7-day subcutaneous administration of recombinant human IL-6 were examined at 3 doses, 50, 100, or 250 mug.kg(-1).d(-1), in rats. Skeletal muscle mass decreased dose-dependently (with increasing dose: in the diaphragm, -10%, P = NS; -15%, P = 0.0561; and -15% P < 0.05; and in the gastrocnemius, -9%, P = NS; -9%, P = NS; and -18%, P < 0.005) because of decreases in cross-sectional area of all fiber types without alterations in diaphragm contractile properties. Cardiovascular variables showed a dose-dependent heart dilatation (for end-diastolic volume: control, 78 muL; moderate dose, 123 muL; and high dose, 137 muL, P < 0.001), reduced end-systolic pressure (control, 113 mm Hg; moderate dose, 87 mm Hg; and high dose, 90 mm Hg; P = 0.037), and decreased myocardial contractility (for preload recruitable stroke work: control, 79 mm Hg; moderate dose, 67 mm Hg; and high dose, 48 mm Hg; P < 0.001). Lung edema was confirmed by an increased wet-to-dry ratio (control, 4.2; moderate dose, 4.6; and high dose, 4.5; P < 0.001) and microscopy findings. These cardiovascular alterations led to decreases in organ blood flow, particularly in the diaphragm (control, 0.56 mL.min(-1).g(-1); moderate dose, 0.21 mL.min(-1).g(-1); and high dose, 0.23 mL.min(-1).g(-1); P = 0.037). In vitro recombinant human IL-6 administration did not cause any alterations in diaphragm force or endurance capacity.Conclusions - IL-6 clearly caused ventilatory and peripheral skeletal muscle atrophy, even after short-term administration. Blood flow redistribution, resulting from the myocardial failure induced by IL-6, was likely responsible for this muscle atrophy, because IL-6 did not exert any direct effect on the diaphragm.