糖皮质激素疗法对肌营养不良症中炎症细胞和树突状细胞的影响。
The effects of glucocorticoid therapy on the inflammatory and dendritic cells in muscular dystrophies.
作者信息
Hussein Mahmoud R, Hamed Sherifa A, Mostafa Mohammed G, Abu-Dief Eman E, Kamel Nageh Fouly, Kandil Mahmoud R
机构信息
Department of Pathology, Assiut University, Assiut, Egypt.
出版信息
Int J Exp Pathol. 2006 Dec;87(6):451-61. doi: 10.1111/j.1365-2613.2006.00470.x.
Various clinical trials have documented the therapeutic benefit of glucocorticoids (GCs) in enhancing muscle strength and slowing disease progression of Duchenne and Becker muscular dystrophies (DMD/BMD). We hypothesized that GCs may have relevance to the differential anti-inflammatory effect on mononuclear inflammatory cells (MICs) and Dendritic cells (DCs) infiltrating the dystrophic muscles. In this prospective study, two muscle biopsies were obtained (before and after 6-month prednisone therapy) from 30 patients with dystrophies (DMD = 18; BMD = 6; and limb girdle muscular dystrophies (LGMD) = 6). MICs and DCs infiltrating the muscles were examined using mouse monoclonal antibodies and immunoperoxidase staining methods. Muscle strength was evaluated monthly by manual testing, motor ability and timed tests. Prednisone therapy was associated with: (i) functional improvement of overall motor disability, in upper limbs of DMD (P < 0.001) and BMD (P < 0.01) and lower limbs of DMD (P < 0.001) and BMD (P < 0.05); (ii) histological improvement such as fibre size variation (DMD, P < 0.01; BMD, P < 0.05), internalization of nuclei (DMD, P < 0.05), degeneration and necrosis (DMD and BMD, P < 0.01), regeneration (DMD, P < 0.001; BMD, P < 0.01) and endomysial connective tissue proliferation (DMD, P < 0.01; BMD, P < 0.05) and (iii) reduction of total MICs (P < 0.01) and DCs (P < 0.01). There was a positive correlation between the degree of improvement in overall motor disability and reduction of DCs numbers (In upper limbs; r = 0.638, P < 0.01 for DMD and r = 0.725, P < 0.01 for BMD, in Lower limbs; r = 0.547, P < 0.05 for DMD and r = 0.576, P < 0.05 for BMD). Such improvements and changes of MICs/DCs were absent in LGMD. In DMD/BMD, prednisone therapeutic effect was associated with reduced MICs and DCs numbers. Whether this therapeutic effect reflects targeting of the deleterious immune response produced by these cells mandates further investigations.
多项临床试验已证明糖皮质激素（GCs）在增强杜氏和贝克型肌营养不良症（DMD/BMD）患者肌肉力量及减缓疾病进展方面具有治疗益处。我们推测，GCs可能与对浸润于营养不良肌肉中的单核炎性细胞（MICs）和树突状细胞（DCs）的不同抗炎作用有关。在这项前瞻性研究中，从30例肌营养不良症患者（DMD = 18例；BMD = 6例；肢带型肌营养不良症（LGMD） = 6例）身上获取了两份肌肉活检样本（泼尼松治疗6个月前后各一份）。使用小鼠单克隆抗体和免疫过氧化物酶染色方法检查浸润肌肉的MICs和DCs。每月通过手动测试、运动能力测试和定时测试评估肌肉力量。泼尼松治疗与以下情况相关：（i）总体运动功能障碍的功能改善，在DMD上肢（P < 0.001）和BMD上肢（P < 0.01）以及DMD下肢（P < 0.001）和BMD下肢（P < 0.05）；（ii）组织学改善，如纤维大小变化（DMD，P < 0.01；BMD，P < 0.05）、核内移（DMD，P < 0.05）、变性和坏死（DMD和BMD，P < 0.01）、再生（DMD，P < 0.001；BMD, P < 0.01）以及肌内膜结缔组织增生（DMD，P < 0.01；BMD，P < 0.05）；（iii）总MICs（P < 0.01）和DCs数量减少（P < 0.01）。总体运动功能障碍的改善程度与DCs数量减少之间存在正相关（在上肢；DMD中r = 0.638，P < 0.01，BMD中r = 0.725，P < 0.01；在下肢；DMD中r = 0.547，P < 0.05，BMD中r = 0.576，P < 0.05）。LGMD患者未出现MICs/DCs的此类改善和变化。在DMD/BMD中，泼尼松的治疗效果与MICs和DCs数量减少有关。这种治疗效果是否反映了针对这些细胞产生的有害免疫反应，还有待进一步研究。
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