Beneficial effects of IL-37 after spinal cord injury in mice
Beneficial effects of IL-37 after spinal cord injury in mice
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DOI：
10.1073/pnas.1523212113
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发表时间：
2016-02-02
影响因子：
11.1
通讯作者：
Lopez-Vales, Ruben
中科院分区：
文献类型：
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作者：
Coll-Miro, Marina;Francos-Quijorna, Isaac;Lopez-Vales, Ruben
IL-37是IL-1家族的成员，广泛减少先天性炎症以及获得性免疫。然而，IL-37的免疫特性是否延伸到中枢神经系统仍然未知。在本研究中，我们进行了小鼠转基因的人IL-37（hIL-37 tg）和野生型（WT）小鼠脊髓挫伤，然后用重组人IL-37（rIL-37）治疗他们。在hIL-37 tg小鼠中，IL-37的表达在未损伤的脊髓中几乎检测不到，但在脊髓损伤（SCI）后24 h和72 h被强烈诱导。与WT小鼠相比，hIL-37 tg小鼠表现出增加的髓鞘和神经元保留和对运动缺陷的保护，包括在强迫跑步机挑战中的2.5倍更高的速度。细胞因子水平降低（例如，IL-6减少80%），沿着较低数量的血液携带的嗜中性粒细胞、巨噬细胞和活化的小胶质细胞。我们在损伤后用全长或加工过的rIL-37单次脊柱内注射治疗WT小鼠，发现IL-37治疗的小鼠在使用Basso小鼠量表的开放场地中具有显著增强的运动技能，并且在机械跑步机上支持更快的速度。用两种形式的rIL-37治疗对SCI后的运动恢复产生类似的有益作用。这项研究提供了新的数据，表明IL-37抑制炎症的临床相关模型的SCI，并表明，rIL-37可能有治疗急性SCI的治疗潜力。
IL-37, a member of the IL-1 family, broadly reduces innate inflammation as well as acquired immunity. Whether the antiinflammatory properties of IL-37 extend to the central nervous system remains unknown, however. In the present study, we subjected mice transgenic for human IL-37 (hIL-37tg) and wild-type (WT) mice to spinal cord contusion injury and then treated them with recombinant human IL-37 (rIL-37). In the hIL-37tg mice, the expression of IL-37 was barely detectable in the uninjured cords, but was strongly induced at 24 h and 72 h after the spinal cord injury (SCI). Compared with WT mice, hIL-37tg mice exhibited increased myelin and neuronal sparing and protection against locomotor deficits, including 2.5-fold greater speed in a forced treadmill challenge. Reduced levels of cytokines (e.g., an 80% reduction in IL-6) were observed in the injured cords of hIL-37tg mice, along with lower numbers of blood-borne neutrophils, macrophages, and activated microglia. We treated WT mice with a single intraspinal injection of either full-length or processed rIL-37 after the injury and found that the IL-37-treated mice had significantly enhanced locomotor skills in an open field using the Basso Mouse Scale, as well as supported faster speed on a mechanical treadmill. Treatment with both forms of rIL-37 led to similar beneficial effects on locomotor recovery after SCI. This study presents novel data indicating that IL-37 suppresses inflammation in a clinically relevant model of SCI, and suggests that rIL-37 may have therapeutic potential for the treatment of acute SCI.