Circulating inflammatory mediators during start of fever in differential diagnosis of gram-negative and gram-positive infections in leukopenic rats
Circulating inflammatory mediators during start of fever in differential diagnosis of gram-negative and gram-positive infections in leukopenic rats
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DOI：
10.1128/cdli.12.9.1085-1093.2005
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发表时间：
2005-09-01
期刊：
影响因子：
--
通讯作者：
Miñano, FJ
中科院分区：
文献类型：
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作者：
Tavares, E;Maldonado, R;Miñano, FJ
革兰氏阴性菌和革兰氏阳性菌感染被认为是化疗后白细胞减少症患者发病和死亡的最重要原因。然而，区分细菌感染和无害的发热事件是困难的。由于感染的典型炎症体征通常不存在，发热通常是感染的唯一体征，因此本研究的目的是评估血清白细胞介素-6（IL-6）、IL-10、巨噬细胞炎性蛋白-2（MIP-2）、降钙素原（PCT）、和C-反应蛋白（CRP）模式在正常和环磷酰胺治疗的发热开始期间识别细菌感染在注射脂多糖（LPS）或胞壁酰二肽（MDP）后，将（白细胞减少）大鼠作为革兰氏阴性和革兰氏阳性细菌感染的模型。我们发现，与正常大鼠相比，免疫抑制的动物表现出显着较高的发热和较少的生产的所有介质，除了IL-6，毒素的挑战。此外，与接受MDP的大鼠相比，接受等效剂量LPS的两组动物均显示出显著更高的发热和血清细胞因子水平的更大增加。此外，与免疫功能正常的大鼠相比，MDP注射后白细胞减少动物的血清IL-6和MIP-2水平没有显著变化。其他血清标志物，如PCT和CRP未能区分两组动物的细菌刺激。这些结果表明，在发热的早期阶段使用分析的血清标志物可以为临床医生提供有用的信息，以排除革兰氏阴性革兰氏阳性感染。
Gram-negative and gram-positive infections have been considered the most important causes of morbidity and mortality in patients with leukopenia following chemotherapy. However, discrimination between bacterial infections and harmless fever episodes is difficult. Because classical inflammatory signs of infection are often absent and fever is frequently the only sign of infection, the aim of this study was to assess the significance of serum interleukin-6 (IL-6), IL-10, macrophage inflammatory protein-2 (MIP-2), procalcitonin (PCT), and C-reactive protein (CRP) patterns in identifying bacterial infections during start of fever in normal and cyclophosphamide-treated (leukopenic) rats following an injection of lipopolysaccharide (LPS) or muramyl dipeptide (MDP) as a model for gram-negative and gram-positive bacterial infections. We found that, compared to normal rats, immunosuppressed animals exhibited significantly higher fevers and lesser production of all mediators, except IL-6, after toxin challenge. Moreover, compared to rats that received MDP, both groups of animals that received an equivalent dose of LPS showed significantly higher fevers and greater increase in serum cytokine levels. Furthermore, in contrast to those in immunocompetent rats, serum levels of IL-6 and MIP-2 were not significantly changed in leukopenic animals after MDP injection. Other serum markers such as PCT and CRP failed to discriminate between bacterial stimuli in both groups of animals. These results suggest that the use of the analyzed serum markers at an early stage of fever could give useful information for the clinician for excluding gram-negative from gram-positive infections.