Schultz Marcus J, van der Poll Tom
Laboratory of Experimental Internal Medicine, and Department of Intensive Care Medicine, Academic Medical Center, Amsterdam, The Netherlands.
Curr Drug Targets Inflamm Allergy. 2004 Mar;3(1):11-7. doi: 10.2174/1568010043483962.
In the last decades several preclinical models for sepsis have been used to study the pathophysiologic processes during sepsis. Although these studies revealed promising immunomodulating agents for the treatment of sepsis, clinical trials evaluating the efficacy of these new agents in septic patients were disappointing. It should be realized that most of the preclinical models for sepsis lack a localized infectious source from which the infection disseminates. Studies on the effects of several immunomodulating strategies have demonstrated strikingly opposite results when using models for sepsis with a more natural route of infection, such as pneumonia, and when using models for sepsis lacking an infectious focus. In this review we will compare models for sepsis and models for pneumonia. We advise to use a combination of models, including models for sepsis and models for localized infections, to test new immunomodulating strategies before starting any clinical trial evaluating a new immunomodulating therapy.
在过去几十年中，几种脓毒症临床前模型被用于研究脓毒症期间的病理生理过程。尽管这些研究揭示了有前景的用于治疗脓毒症的免疫调节药物，但评估这些新药在脓毒症患者中疗效的临床试验却令人失望。应该认识到，大多数脓毒症临床前模型缺乏感染从中播散的局部感染源。当使用具有更自然感染途径的脓毒症模型（如肺炎模型）以及缺乏感染灶的脓毒症模型时，关于几种免疫调节策略效果的研究已显示出截然不同的结果。在本综述中，我们将比较脓毒症模型和肺炎模型。我们建议在启动任何评估新免疫调节疗法的临床试验之前，使用包括脓毒症模型和局部感染模型在内的多种模型组合来测试新的免疫调节策略。
