Spinal Cord Injury Team, Robarts Research Institute, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada.
J Neurotrauma. 2012 May 20;29(8):1626-37. doi: 10.1089/neu.2011.2190. Epub 2012 Feb 29.
Abstract The systemic inflammatory response syndrome (SIRS) follows spinal cord injury (SCI) and causes damage to the lungs, kidney, and liver due to an influx of inflammatory cells from the circulation. After SCI in rats, the SIRS develops within 12 h and is sustained for at least 3 days. We have previously shown that blockade of CD11d/CD18 integrin reduces inflammation-driven secondary damage to the spinal cord. This treatment reduces the SIRS after SCI. In another study we found that blockade of α4β1 integrin limited secondary cord damage more effectively than blockade of CD11d/CD18. Therefore we considered it important to assess the effects of anti-α4β1 treatment on the SIRS in the lung, kidney, and liver after SCI. An anti-α4 antibody was given IV at 2 h after SCI at the fourth thoracic segment and the effects on the organs were evaluated at 24 h post-injury. The migration of neutrophils into the lungs and liver was markedly reduced and all three organs contained fewer macrophages. In the lungs and liver, the activation of the oxidative enzymes myeloperoxidase (MPO), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and gp91(phox), the production of free radicals, lipid peroxidation, and cell death were substantially and similarly reduced. Treatment effects were less robust in the kidney. Overall, the efficacy of the anti-α4β1 treatment did not differ greatly from that of the anti-CD11d antibody, although details of the results differed. The SIRS after SCI impedes recovery, and attenuation of the SIRS with an anti-integrin treatment is an important, clinically-relevant finding.
摘要 全身性炎症反应综合征（SIRS）发生在脊髓损伤（SCI）之后，由于炎症细胞从循环中涌入，会对肺部、肾脏和肝脏造成损伤。在大鼠 SCI 后，SIRS 在 12 小时内发展，并至少持续 3 天。我们之前已经表明，阻断 CD11d/CD18 整合素可以减少炎症驱动的脊髓继发性损伤。这种治疗方法可以减少 SCI 后的 SIRS。在另一项研究中，我们发现阻断 α4β1 整合素比阻断 CD11d/CD18 更有效地限制继发性脊髓损伤。因此，我们认为评估抗-α4β1 治疗对 SCI 后肺、肾和肝中 SIRS 的影响非常重要。在第 4 胸椎段 SCI 后 2 小时给予 IV 抗-α4 抗体，并在损伤后 24 小时评估对器官的影响。中性粒细胞向肺和肝脏的迁移明显减少，所有三个器官中的巨噬细胞数量也减少。在肺和肝脏中，髓过氧化物酶（MPO）、诱导型一氧化氮合酶（iNOS）、环氧化酶-2（COX-2）和 gp91(phox) 的氧化酶活性、自由基的产生、脂质过氧化和细胞死亡都显著减少。在肾脏中，治疗效果较弱。总体而言，抗-α4β1 治疗的疗效与抗-CD11d 抗体的疗效没有太大区别，尽管结果细节有所不同。SCI 后的 SIRS 会阻碍恢复，而使用整合素抑制剂减轻 SIRS 是一个重要的、具有临床相关性的发现。
