Remick Daniel G, Bolgos Gerald, Copeland Shannon, Siddiqui Javed
Department of Pathology, University of Michigan, Ann Arbor, MI 48109-0602, USA.
Infect Immun. 2005 May;73(5):2751-7. doi: 10.1128/IAI.73.5.2751-2757.2005.
Previous studies have suggested that interleukin-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.
先前的研究表明，白细胞介素-6（IL-6）既是脓毒症严重程度的标志物，也是其介导因子。我们测试了白细胞介素6基因敲除（IL-6KO）小鼠是否更易死于盲肠结扎穿孔诱导的脓毒症。对IL-6KO和野生型（WT）小鼠施加不同程度的脓毒症严重程度。通过补液和使用适当的抗生素给予生理支持。在脓毒症发作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，脓毒症严重程度增加导致更高且更快速的死亡率。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作6小时后血浆IL-6水平都很高，而IL-6KO小鼠的血浆IL-6水平接近或低于检测下限。在WT小鼠中，血浆IL-6>3000 pg/ml的小鼠死亡率显著更高。注定在脓毒症早期死亡的IL-6KO和WT小鼠在最初24小时内体重都有显著且几乎相同的增加。然而，在后期，WT小鼠的体重减轻明显大于KO小鼠。KO小鼠在严重脓毒症的最初24小时内未出现WT小鼠中常见的特征性体温过低。这些数据表明，IL-6是脓毒症疾病严重程度的标志物，并且确实调节一些生理反应，但完全缺乏IL-6并不会改变脓毒症导致的死亡率。
