Proinflammatory cytokine surge after injury stimulates an airway immunoglobulin a increase.
Proinflammatory cytokine surge after injury stimulates an airway immunoglobulin a increase.
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DOI：
10.1097/ta.0b013e3181c45284
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发表时间：
2010-10
期刊：
影响因子：
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通讯作者：
Kudsk KA
中科院分区：
文献类型：
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作者：
Jonker MA;Sano Y;Hermsen JL;Lan J;Kudsk KA
损伤刺激严重损伤患者的先天气道伊加反应，这也发生在小鼠中。肿瘤坏死因子-α（TNF-α）和白细胞介素-1 β（IL-1β）刺激多聚免疫球蛋白受体（pIgR）的产生，pIgR是将免疫球蛋白A（伊加）转运至粘膜表面所需的蛋白质。阻断TNF-α和IL-1β可消除气道对损伤的IgA反应。IL-6刺激B细胞在粘膜部位分化为分泌伊加的浆细胞。我们研究了小鼠损伤后TNF-α、IL-1β和IL-6的局部和全身动力学。我们还假设注射外源性TNF-α、IL-1β和IL-6可以复制气道伊加对损伤的反应。实验一：将雄性癌症研究所（ICR）小鼠随机分配至未受伤的对照组（n = 8）或手术应激组，其中剖腹术和颈部切口在受伤后1、2、3、5或8小时处死（n = 8/组）。ELISA法检测支气管肺泡灌洗（BAL）及血清TNF-α、IL-1β、IL-6水平。实验二：将雄性ICR小鼠随机分配至未损伤对照组（n = 6）、损伤组（手术应激，除腹膜保持完整外，与实验1相似，n = 6）或细胞因子注射组（腹膜内注射重组TNF-α、IL-1β和IL-6）。损伤后2小时处死动物，通过ELISA分析鼻气道灌洗液和支气管肺泡灌洗液伊加。实验1：BALTNF-α、IL-1β和IL-6水平在伤后3 h和8 h与对照组相比呈双峰模式升高（p<0.05）。血清IL-6在3小时没有增加，但到5小时与对照相比确实显示出显著增加（p<0.05）。血清TNF-α和IL-1β水平无变化。实验二：与对照相比，损伤和TNF-α、IL-1β和IL-6细胞因子的组合注射均显著增加了气道灌洗（BAL+NAL）中的伊加水平（两者均为p<0.01）。损伤后气道TNF-α、IL-1β和IL-6水平以双峰模式增加，在3和8小时达到峰值，与血清变化不一致。8小时的峰值与损伤后气道伊加的已知增加一致。腹腔注射外源性TNF-α、IL-1β和IL-6的组合复制了损伤后气道伊加的增加。这种效果在单独的细胞因子注射中没有观察到。
Injury stimulates an innate airway IgA response in severely injured patients, which also occurs in mice. Tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) stimulate the production of polymeric immunoglobulin receptor (pIgR), the protein required to transport immunoglobulin A (IgA) to mucosal surfaces. Blockade of TNF-α and IL-1β eliminates the airway IgA response to injury. IL-6 stimulates differentiation of B cells into IgA secreting plasma cells at mucosal sites. We investigated the local and systemic kinetics of TNF-α, IL-1β, and IL-6 after injury in mice. We also hypothesized that injection of exogenous TNF-α, IL-1β, and IL-6 would replicate the airway IgA response to injury. Experiment 1: Male Institute of Cancer Research (ICR) mice were randomized to uninjured controls (n = 8) or to surgical stress with laparotomy and neck incisions with sacrifice at 1, 2, 3, 5, or 8 hours after injury (n = 8/group). Bronchoalveolar lavage (BAL) and serum levels of TNF-α, IL-1β, and IL-6 were analyzed by ELISA. Experiment 2: Male ICR mice were randomized to uninjured controls (n = 6), Injury (surgical stress that was similar to expt 1 except the peritoneum was left intact, n = 6), or Cytokine injection with intraperitoneal injection of recombinant TNF-α, IL-1β, and IL-6. Animals were sacrificed at 2 hours after injury and nasal airway lavage and bronchoalveolar lavage IgA were analyzed by ELISA. Experiment 1: BAL TNF-α, IL-1β and IL-6 levels increased in bimodal pattern after injury at 3 h and 8 h vs controls (p<0.05). Serum IL-6 did not increase at 3 h, but did show a significant increase by 5 h vs control (p<0.05). Serum levels of TNF-α and IL-1β did not change. Experiment 2: Both Injury and combination TNF-α, IL-1β and IL-6 cytokine injection significantly increased IgA levels in airway lavage (BAL+NAL) compared to control (p<0.01 for both). Airway levels of TNF-α, IL-1β, and IL-6 increase in a bimodal pattern after injury with peaks at 3 and 8 hours that do not correspond to serum changes. The peak at 8 hours is consistent with the known increase in airway IgA after injury. Intraperitoneal injection of a combination exogenous TNF-α, IL-1β, and IL-6 replicates the airway IgA increase after injury. This effect is not seen with individual cytokine injections.