Interleukin-15 administration improves diaphragm muscle pathology and function in dystrophic mdx mice
Interleukin-15 administration improves diaphragm muscle pathology and function in dystrophic mdx mice
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DOI：
10.1016/s0002-9440(10)62333-4
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发表时间：
2005-04-01
影响因子：
6
通讯作者：
Lynch, GS
中科院分区：
文献类型：
--
作者：
Harcourt, LJ;Holmes, AG;Lynch, GS
白介素15是一种在骨骼肌中表达的细胞因子，已被证明在体外具有肌肉合成代谢作用，并能减缓癌症恶病质大鼠的肌肉萎缩。IL-15是否具有治疗杜氏肌营养不良症(DMD)等疾病的潜力尚不清楚。我们研究了IL-15的应用是否能改善DMD动物模型MDX小鼠横隔肌的营养不良病理。四周的IL-15治疗改善了横隔膜的强度，这是一个非常有意义的发现，因为呼吸功能是DMD死亡的预测因素。横隔膜功能增强与肌纤维横截面积增加和胶原渗出减少有关。IL-15的应用与T细胞群体的变化或泛素蛋白酶体途径的特定成分的变化无关。为了确定IL-15对肌纤维再生的影响，对IL-15处理和未处理的野生型小鼠的肌肉进行了肌肉毒性损伤，并对其功能恢复进行了评估。IL-15有轻微的合成代谢作用，在2天和6天后纤维横截面积增加，但在10天后不再增加。我们的研究结果表明，IL-15的应用改善了营养不良肌肉的病理生理学，并强调了IL-15在治疗神经肌肉疾病，特别是肌肉萎缩的治疗中可能的作用。
interleukin (IL)-15, a cytokine expressed in skeletal muscle, has been shown to have muscle anabolic effects in vitro and to slow muscle wasting in rats with cancer cachexia. Whether IL-15 has therapeutic potential for diseases such as Duchenne muscular dystrophy (DMD) is unknown. We examined whether IL-15 administration could ameliorate the dystrophic pathology in the diaphragm muscle of the mdx mouse, an animal model for DMD. Four weeks of IL-15 treatment improved diaphragm strength, a highly significant finding because respiratory function is a mortality predictor in DMD. Enhanced diaphragm function was associated with increased muscle fiber cross-sectional area and decreased collagen infiltration. IL-15 administration was not associated with changes in T-cell populations or alterations in specific components of the ubiquitin proteasome pathway. To determine the effects of IL-15 on myofiber regeneration, muscles of IL-15-treated and untreated wild-type mice were injured myotoxically, and their functional recovery was assessed. IL-15 had a mild anabolic effect, increasing fiber cross-sectional area after 2 and 6 days but not after 10 days. Our findings demonstrate that IL-15 administration improves the pathophysiology of dystrophic muscle and highlight a possible therapeutic role for IL-15 in the treatment of neuromuscular disorders especially in which muscle wasting is indicated.