Endogenous Expression of Interleukin-4 Regulates Macrophage Activation and Confines Cavity Formation After Traumatic Spinal Cord Injury
Endogenous Expression of Interleukin-4 Regulates Macrophage Activation and Confines Cavity Formation After Traumatic Spinal Cord Injury
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DOI：
10.1002/jnr.22411
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发表时间：
2010-08-15
影响因子：
4.2
通讯作者：
Kim, Byung G.
中科院分区：
文献类型：
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作者：
Lee, Seung Ihm;Jeong, Soo Ryeong;Kim, Byung G.
创伤性脊髓损伤（SCI）引发多种类型细胞和细胞因子参与的炎症反应。几种促炎细胞因子在脊髓损伤后上调，在决定继发性组织损伤程度中起关键作用。然而，人们对抗炎细胞因子及其在脊髓损伤中的作用知之甚少。最近的研究表明，抗炎细胞因子白介素-4 （IL-4）在中枢神经系统炎症中表达并发挥多种调节作用。我们在本研究中发现，IL-4在大鼠挫伤性脊髓损伤后24小时高表达，此后下降，同时IL-4受体亚基IL-40 α上调。大多数产生il -4的细胞是髓过氧化物酶阳性的中性粒细胞。在挫伤脊髓内注射抗IL-4的中和抗体对IL-1 β、IL-6、肿瘤坏死因子-a等促炎细胞因子和IL-10、转化生长因子- β等抗炎细胞因子的表达水平无显著影响。相反，损伤后7天，IL-4活性的衰减导致ed1阳性巨噬细胞沿背侧侧的激活程度显著增加。巨噬细胞活化增强之前，单核细胞趋化蛋白-1 （MCP-1/CCL2）水平升高。最后，IL-4中和在损伤后4周导致更广泛的空化。这些结果表明，抗炎细胞因子IL-4的内源性表达调节了急性巨噬细胞的激活程度，并限制了脊髓损伤后继发性空洞的形成。(C) 2010 Wiley-Liss, Inc。
Traumatic spinal cord injury (SCI) triggers inflammatory reactions in which various types of cells and cytokines are involved. Several proinflammatory cytokines are up-regulated after SCI and play crucial roles in determining the extent of secondary tissue damage. However, relatively little is known about antiinflammatory cytokines and their roles in spinal cord trauma. Recent studies have shown that an antiinflammatory cytokine, interleukin-4 (IL-4), is expressed and exerts various modulatory effects in CNS inflammation. We found in the present study that IL-4 was highly expressed at 24 hr after contusive SCI in rats and declined thereafter, with concurrent up-regulation of IL-4 receptor subunit IL-40 alpha. The majority of IL-4-producing cells were myeloperoxidase-positive neutrophils. Injection of neutralizing antibody against IL-4 into the contused spinal cord did not significantly affect the expression levels of proinflammatory cytokines such as IL-1 beta, IL-6, and tumor necrosis factor-a or other antiinflammatory cytokines such as IL-10 and transforming growth factor-beta. Instead, attenuation of IL-4 activity led to a marked increase in the extent of ED1-positive macrophage activation along the rostrocaudal extent at 7 days after injury. The enhanced macrophage activation was preceded by an increase in the level of monocyte chemoattractant protein-1 (MCP-1/CCL2). Finally, IL-4 neutralization resulted in more extensive cavitation at 4 weeks after injury. These results suggest that endogenous expression of antiinflammatory cytokine IL-4 regulates the extent of acute macrophage activation and confines the ensuing secondary cavity formation after spinal cord trauma. (C) 2010 Wiley-Liss, Inc.