Costa Luis H A, Trajano Isis P, Passaglia Patricia, Branco Luiz G S
Department of Oral and Basic Biology, School of Dentistry of Ribeirão Preto - University of São Paulo, Avenida Bandeirantes, Ribeirão Preto, SP, 14040-902, Brazil.
Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA.
Intensive Care Med Exp. 2024 Nov 10;12(1):100. doi: 10.1186/s40635-024-00687-8.
Sepsis remains a major global health concern due to its high prevalence and mortality. Changes in body temperature (Tb), such as hypothermia or fever, are diagnostic indicators and play a crucial role in the pathophysiology of sepsis. This study aims to characterize the thermoregulatory mechanisms during sepsis using the cecal ligation and puncture (CLP) model and explore how sepsis severity and ambient temperature (Ta) influence Tb regulation and mortality. Rats were subjected to mild or severe sepsis by CLP while housed at thermoneutral (28 °C) or subthermoneutral (22 °C) Ta, and their Tb was monitored for 12 h. Blood and hypothalamus were collected for cytokines and prostaglandin E (PGE) analysis.
At 28 °C, febrile response magnitude correlated with sepsis severity and inflammatory response, with tail vasoconstriction as the primary heat retention mechanism. At 22 °C, Tb was maintained during mild sepsis but dropped during severe sepsis, linked to reduced UCP1 expression in brown adipose tissue and less effective vasoconstriction. Despite differences in thermoregulatory responses, both Ta conditions induced a persistent inflammatory response and increased hypothalamic PGE production. Notably, mortality in severe sepsis was significantly higher at 28 °C (80%) compared to 22 °C (0%).
Our findings reveal that ambient temperature and the inflammatory burden critically influence thermoregulation and survival during early sepsis. These results emphasize the importance of considering environmental factors in preclinical sepsis studies. Although rodents in experimental settings are often adapted to cold environments, these conditions may not fully translate to human sepsis, where cold adaptation is rare. Thus, researchers should carefully consider these variables when designing experiments and interpreting translational implications.
由于脓毒症的高发病率和死亡率，它仍然是一个主要的全球健康问题。体温（Tb）的变化，如体温过低或发热，是诊断指标，在脓毒症的病理生理学中起着关键作用。本研究旨在使用盲肠结扎和穿刺（CLP）模型来描述脓毒症期间的体温调节机制，并探讨脓毒症严重程度和环境温度（Ta）如何影响Tb调节和死亡率。将大鼠通过CLP诱导为轻度或重度脓毒症，同时饲养在热中性（28°C）或亚热中性（22°C）的Ta环境中，并监测它们的Tb达12小时。采集血液和下丘脑用于细胞因子和前列腺素E（PGE）分析。
在28°C时，发热反应强度与脓毒症严重程度和炎症反应相关，尾部血管收缩是主要的产热机制。在22°C时，轻度脓毒症期间Tb得以维持，但重度脓毒症期间Tb下降，这与棕色脂肪组织中UCP1表达降低和血管收缩效果减弱有关。尽管体温调节反应存在差异，但两种Ta条件均诱导了持续的炎症反应并增加了下丘脑PGE的产生。值得注意的是，重度脓毒症在28°C时的死亡率（80%）显著高于22°C时（0%）。
我们的研究结果表明，环境温度和炎症负荷对早期脓毒症期间的体温调节和生存有至关重要的影响。这些结果强调了在临床前脓毒症研究中考虑环境因素的重要性。尽管实验环境中的啮齿动物通常适应寒冷环境，但这些情况可能无法完全转化为人类脓毒症，因为人类很少有冷适应情况。因此，研究人员在设计实验和解释转化意义时应仔细考虑这些变量。
