Koo D J, Zhou M, Jackman D, Cioffi W G, Bland K I, Chaudry I H, Wang P
Center for Surgical Research and Department of Surgery, Brown University School of Medicine and Rhode Island Hospital, Middle House II, 593 Eddy Street, Providence, RI 02903, USA.
Biochim Biophys Acta. 1999 Aug 30;1454(3):289-95. doi: 10.1016/s0925-4439(99)00045-9.
Although studies have shown that the gut is capable of being a cytokine-producing organ and that the proinflammatory cytokines TNF-alpha, IL-1beta, and IL-6 are upregulated following the onset of sepsis, it remains unknown whether the gut is indeed the major source of the increased cytokine production under such conditions. To determine this, male rats were subjected to cecal ligation and puncture (CLP, a model of polymicrobial sepsis) or sham operation followed by the administration of normal saline solution subcutaneously (i.e., fluid resuscitation). Systemic and portal blood samples were taken simultaneously at 2, 5, 10, or 20 h after CLP or sham operation. Plasma levels of TNF-alpha, IL-1beta, and IL-6 were determined using an enzyme-linked immunosorbent assay. In additional animals, the small intestine was harvested at 10 h after CLP or sham operation and examined for TNF-alpha, IL-1beta, and IL-6 gene expression by RT-PCR. The results indicate that the levels of TNF-alpha, IL-1beta, and IL-6 in both systemic and portal blood samples were significantly elevated during sepsis with the exception that the increase in IL-1beta was not significant at 2 h after CLP. However, there were no significant differences in the levels of those proinflammatory cytokines between systemic and portal blood at any points after the onset of sepsis. Moreover, there were no significant alterations in the proinflammatory cytokine gene expression in the small intestine at 10 h after CLP. Since the levels of TNF-alpha, IL-1beta, and IL-6 were not significantly increased in portal blood as compared to systemic blood and since there was no upregulation of gene expression for these cytokines, it appears that organs other than the gut are responsible for the upregulated proinflammatory cytokines during polymicrobial sepsis.
尽管研究表明肠道能够成为产生细胞因子的器官，并且在脓毒症发作后促炎细胞因子肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）和白细胞介素-6（IL-6）会上调，但在这种情况下肠道是否确实是细胞因子产生增加的主要来源仍不清楚。为了确定这一点，对雄性大鼠进行盲肠结扎和穿刺（CLP，一种多微生物脓毒症模型）或假手术，然后皮下注射生理盐水溶液（即液体复苏）。在CLP或假手术后2、5、10或20小时同时采集全身和门静脉血样。使用酶联免疫吸附测定法测定血浆中TNF-α、IL-1β和IL-6的水平。在另外的动物中，在CLP或假手术后10小时采集小肠，通过逆转录聚合酶链反应（RT-PCR）检测TNF-α、IL-1β和IL-6基因表达。结果表明，在脓毒症期间，全身和门静脉血样中TNF-α、IL-1β和IL-6的水平均显著升高，但CLP后2小时IL-1β的升高不显著。然而，脓毒症发作后任何时间点，全身血和门静脉血中这些促炎细胞因子的水平均无显著差异。此外，CLP后10小时小肠中促炎细胞因子基因表达无显著变化。由于与全身血相比，门静脉血中TNF-α、IL-1β和IL-6的水平没有显著升高，并且这些细胞因子的基因表达没有上调，因此看来在多微生物脓毒症期间，肠道以外的器官是促炎细胞因子上调的原因。
