骨折和创伤性脑损伤后的早期免疫反应改变。

INTRODUCTION: Clinical and preclinical data suggest accelerated bone fracture healing in subjects with an additional traumatic brain injury (TBI). Mechanistically, altered metabolism and neuro-endocrine regulations have been shown to influence bone formation after combined fracture and TBI, thereby increasing the bone content in the fracture callus. However, the early inflammatory response towards fracture and TBI has not been investigated in detail so far. This is of great importance, since the early inflammatory phase of fracture healing is known to be essential for the initiation of downstream regenerative processes for adequate fracture repair. METHODS: Therefore, we analyzed systemic and local inflammatory mediators and immune cells in mice which were exposed to fracture only or fracture + TBI 6h and 24h after injury. RESULTS: We found a dysregulated systemic immune response and significantly fewer neutrophils and mast cells locally in the fracture hematoma. Further, local CXCL10 expression was significantly decreased in the animals with combined trauma, which correlated significantly with the reduced mast cell numbers. DISCUSSION: Since mast cells and mast cell-derived CXCL10 have been shown to increase osteoclastogenesis, the reduced mast cell numbers might contribute to higher bone content in the fracture callus of fracture + TBI mice due to decreased callus remodeling.

简介：临床和临床前数据表明，合并创伤性脑损伤（TBI）的患者骨折愈合速度加快。从机制上讲，代谢和神经内分泌调节的改变被证明会影响骨折合并 TBI 后的骨形成，从而增加骨折痂中的骨含量。然而，迄今为止，尚未详细研究骨折和 TBI 后的早期炎症反应。这一点非常重要，因为众所周知，骨折愈合的早期炎症阶段对于启动适当的骨折修复的下游再生过程至关重要。

方法：因此，我们分析了仅骨折或骨折+TBI 后 6 小时和 24 小时的小鼠的系统和局部炎症介质和免疫细胞。

结果：我们发现全身免疫反应失调，骨折血肿局部的中性粒细胞和肥大细胞明显减少。此外，在合并创伤的动物中，局部 CXCL10 的表达显著降低，与肥大细胞数量减少显著相关。

讨论：由于肥大细胞和肥大细胞衍生的 CXCL10 已被证明可增加破骨细胞生成，因此骨折+TBI 小鼠骨折痂中破骨细胞数量减少可能导致骨含量增加，因为骨痂重塑减少。