Department of Basic and Oral Biology, School of Dentistry of Ribeirão Preto, University of Sao Paulo, Ribeirão Preto, SP 14040-904, Brazil.
Department of Neurosciences and Behavioral Sciences of Ribeirão Preto Medical School, University of Sao Paulo, Ribeirão Preto, SP 14040-900, Brazil.
Int J Mol Sci. 2019 Aug 30;20(17):4255. doi: 10.3390/ijms20174255.
Sepsis is a syndrome characterized by a dysregulated inflammatory response, cellular stress, and organ injury. Sepsis is the main cause of death in intensive care units worldwide, creating need for research and new therapeutic strategies. Heat shock protein (HSP) analyses have recently been developed in the context of sepsis. HSPs have a cytoprotection role in stress conditions, signal to immune cells, and activate the inflammatory response. Hence, HSP analyses have become an important focus in sepsis research, including the investigation of HSPs targeted by therapeutic agents used in sepsis treatment. Many therapeutic agents have been tested, and their HSP modulation showed promising results. Nonetheless, the heterogeneity in experimental designs and the diversity in therapeutic agents used make it difficult to understand their efficacy in sepsis treatment. Therefore, future investigations should include the analysis of parameters related to the early and late immune response in sepsis, HSP localization (intra or extracellular), and time to the onset of treatment after sepsis. They also should consider the differences in experimental sepsis models. In this review, we present the main results of studies on therapeutic agents in targeting HSPs in sepsis treatment. We also discuss limitations and possibilities for future investigations regarding HSP modulators.
脓毒症是一种以炎症反应失调、细胞应激和器官损伤为特征的综合征。脓毒症是全球重症监护病房死亡的主要原因,因此需要研究和新的治疗策略。热休克蛋白 (HSP) 分析最近在脓毒症的背景下得到了发展。在应激条件下,HSP 具有细胞保护作用,向免疫细胞发出信号,并激活炎症反应。因此,HSP 分析已成为脓毒症研究的一个重要焦点,包括研究用于脓毒症治疗的治疗剂靶向的 HSP。已经测试了许多治疗剂,它们对 HSP 的调节显示出有希望的结果。然而,实验设计的异质性和治疗剂的多样性使得难以理解它们在脓毒症治疗中的疗效。因此,未来的研究应包括分析与脓毒症早期和晚期免疫反应相关的参数、HSP 的定位(细胞内或细胞外)以及脓毒症后开始治疗的时间。它们还应考虑实验性脓毒症模型的差异。在这篇综述中,我们介绍了针对脓毒症治疗中 HSP 的治疗剂的主要研究结果。我们还讨论了 HSP 调节剂未来研究的局限性和可能性。