Role of interleukin-6 in mortality from and physiologic response to sepsis
Role of interleukin-6 in mortality from and physiologic response to sepsis
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DOI：
10.1128/iai.73.5.2751-2757.2005
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发表时间：
2005-05-01
影响因子：
3.1
通讯作者：
Siddiqui, J
中科院分区：
文献类型：
--
作者：
Remick, DG;Bolgos, G;Siddiqui, J
先前的研究表明，白细胞介素-6 （IL-6）是脓毒症严重程度的标志物和中介。我们检测白细胞介素6敲除（IL-6KO）小鼠是否更容易发生盲肠结扎和穿刺引起的脓毒症死亡。IL-6KO和野生型（WT）小鼠的脓毒症严重程度逐渐增加。生理支持给予液体和适当的抗生素。在脓毒症发生6小时后测定血浆IL-6水平，并在第2天进行完整的血液学分析。正如预期的那样，脓毒症严重程度的增加导致了更大、更快的死亡率。然而，IL-6KO和WT小鼠的死亡率几乎相同。所有WT脓毒症小鼠在脓毒症发病6 h后血浆IL-6水平均较高，IL-6KO接近或低于检测下限。在WT小鼠中，血浆IL-6≥3000 pg/ml的小鼠死亡率显著增高。在败血症早期阶段死亡的IL-6KO和WT小鼠在前24小时内都有大量几乎相同的体重增加。然而，在后期，WT小鼠的体重下降明显大于KO小鼠。KO小鼠在WT小鼠中观察到的严重败血症的前24小时内没有出现特征性的体温过低。这些数据表明，IL-6是脓毒症中疾病严重程度的标志，确实调节了一些生理反应，但完全缺乏IL-6并不会改变脓毒症的死亡率。
Previous studies have suggested that interieukin-6 (IL-6) serves as both a marker and a mediator for the severity of sepsis. We tested whether interleukin 6 knockout (IL-6KO) mice were more susceptible to sepsis mortality induced by cecal ligation and puncture. IL-6KO and wild-type (WT) mice were subjected to increasing degrees of sepsis severity. Physiologic support was given with fluids and appropriate antibiotics. Plasma IL-6 levels were determined 6 h after the onset of sepsis, and a complete hematologic profile was performed on day 2. As expected, increasing sepsis severity resulted in greater and more rapid mortality. However, the mortality was nearly identical in the IL-6KO and WT mice. All WT septic mice had high plasma levels of IL-6 6 h after the onset of sepsis, while IL-6KO were near or below the lower limit of detection. Among the WT mice, mortality was significantly higher in mice with plasma IL-6 > 3,000 pg/ml. Both IL-6KO and WT mice destined to die in the early stages of sepsis had substantial and nearly identical weight gain in the first 24 h. However, at later stages the WT mice had significantly greater weight loss than the KO mice. The KO mice failed to develop the characteristic hypothermia within the first 24 h of severe sepsis routinely observed in the WT mice. These data demonstrate that IL-6 serves as a marker of disease severity in sepsis and does modulate some physiologic responses, but complete lack of IL-6 does not does not alter mortality due to sepsis.