Xiao Hongyan, Siddiqui Javed, Remick Daniel G
Department of Pathology, University of Michigan, 2210 Medical Science I Building, 1301 Catherine Road, Ann Arbor, MI 48109-0602, USA.
Infect Immun. 2006 Sep;74(9):5227-35. doi: 10.1128/IAI.01220-05.
A recent hypothesis postulates that sepsis moves through different phases, with periods of enhanced inflammation alternating with periods of immune suppression. In this study we determined the levels of inflammation present during early and late septic deaths to examine whether death was due to hyperinflammation or immunosuppression. The murine model of sepsis induced by cecal ligation and puncture (CLP) was used. Complete blood counts, plasma interleukin-6 (IL-6) levels, and body weights were determined. Mice that died within the first 4 days had increased plasma levels of IL-6, indicating that there was activation of the immune system. Cecal resection on day 4 after CLP resulted in decreased abscess size, lower circulating neutrophil counts, decreased anemia, and improved survival compared to the results for mice that received only antibiotic and fluid therapy. All of the mice that died in the chronic phase of infection (after day 4) had positive peritoneal cultures containing significantly more bacteria than the cultures for surviving mice. After day 4, none of the surviving mice exhibited increases in the plasma levels of IL-6. Dying mice exhibited mixed IL-6 responses; for 41% of the mice there was never an increase in the IL-6 levels in the chronic phase, while for other mice the levels of IL-6 transiently increased prior to death. Peritoneal macrophages were obtained in the late phase of sepsis from moribund and healthy mice and were stimulated ex vivo. The cells from the moribund mice produced significantly less IL-6 than the cells obtained from healthy mice produced. These results indicate that in mice that die in the early phase there is uniformly increased inflammation. However, during the chronic phase of sepsis, some mice die with evidence of immunosuppression (increased bacterial growth and low IL-6 levels), while other mice die with immunostimulation (high IL-6 levels and bacterial growth). Determining the inflammatory status of individual patients may help guide appropriate, targeted therapy.
最近有假说认为，脓毒症会经历不同阶段，炎症增强期与免疫抑制期交替出现。在本研究中，我们测定了早期和晚期脓毒症死亡期间的炎症水平，以检查死亡是由于炎症反应过度还是免疫抑制。采用盲肠结扎和穿刺（CLP）诱导的小鼠脓毒症模型。测定全血细胞计数、血浆白细胞介素-6（IL-6）水平和体重。在最初4天内死亡的小鼠血浆IL-6水平升高，表明免疫系统被激活。与仅接受抗生素和液体治疗的小鼠相比，CLP术后第4天进行盲肠切除术可使脓肿大小减小、循环中性粒细胞计数降低、贫血减轻且存活率提高。所有在感染慢性期（第4天后）死亡的小鼠腹膜培养均为阳性，且培养出的细菌数量明显多于存活小鼠。第4天后，存活小鼠的血浆IL-6水平均未升高。濒死小鼠的IL-6反应各异；41%的小鼠在慢性期IL-6水平从未升高，而其他小鼠在死亡前IL-6水平短暂升高。在脓毒症晚期，从濒死和健康小鼠获取腹膜巨噬细胞并进行体外刺激。濒死小鼠的细胞产生的IL-6明显少于健康小鼠的细胞。这些结果表明，在早期死亡的小鼠中炎症反应一致增强。然而，在脓毒症慢性期，一些小鼠死于免疫抑制（细菌生长增加和IL-6水平低）的证据，而其他小鼠死于免疫刺激（IL-6水平高和细菌生长）。确定个体患者的炎症状态可能有助于指导适当的靶向治疗。
