Rudaya Alla Y, Steiner Alexandre A, Robbins Jared R, Dragic Alexander S, Romanovsky Andrej A
Systemic Inflammation Laboratory, Trauma Research, St. Joseph's Hospital and Medical Center, 350 W. Thomas Rd., Phoenix, Arizona 85013, USA.
Am J Physiol Regul Integr Comp Physiol. 2005 Nov;289(5):R1244-52. doi: 10.1152/ajpregu.00370.2005. Epub 2005 Aug 4.
Most published studies of thermoregulatory responses of mice to LPS involved a stressful injection of LPS, were run at a poorly controlled and often subneutral ambient temperature (T(a)), and paid little attention to the dependence of the response on the LPS dose. These pitfalls have been overcome in the present study. Male C57BL/6 mice implanted with jugular vein catheters were kept in an environmental chamber at a tightly controlled T(a). The relationship between the T(a)s used and the thermoneutral zone of the mice was verified by measuring tail skin temperature, either by infrared thermography or thermocouple thermometry. Escherichia coli LPS in a wide dose range (10(0)-10(4) microg/kg) was administered through an extension of the jugular catheter from outside the chamber. The responses observed were dose dependent. At a neutral T(a), low (just suprathreshold) doses of LPS (10(0)-10(1) microg/kg) caused a monophasic fever. To a slightly higher dose (10(1.5) microg/kg), the mice responded with a biphasic fever. To even higher doses (10(1.75)-10(4) microg/kg), they responded with a polyphasic fever, of which three distinct phases were identified. The dose dependence and dynamics of LPS fever in the mouse appeared to be remarkably similar to those seen in the rat. However, the thermoregulatory response of mice to LPS in a subthermoneutral environment is remarkably different from that of rats. Although very high doses of LPS (10(4) microg/kg) did cause a late (latency, approximately 3 h) hypothermic response in mice, the typical early (latency, 10-30 min) hypothermic response seen in rats did not occur. The present investigation identifies experimental conditions to study LPS-induced mono-, bi-, and polyphasic fevers and late hypothermia in mice and provides detailed characteristics of these responses.
大多数已发表的关于小鼠对脂多糖（LPS）体温调节反应的研究涉及有压力的LPS注射，实验在控制不佳且通常低于中性的环境温度（Ta）下进行，并且很少关注反应对LPS剂量的依赖性。本研究克服了这些缺陷。将植入颈静脉导管的雄性C57BL/6小鼠置于环境舱中，严格控制Ta。通过红外热成像或热电偶测温法测量尾皮肤温度，验证所用Ta与小鼠热中性区之间的关系。通过颈静脉导管从舱外延伸给予宽剂量范围（10⁰ - 10⁴ μg/kg）的大肠杆菌LPS。观察到的反应具有剂量依赖性。在中性Ta下，低剂量（刚好高于阈值）的LPS（10⁰ - 10¹ μg/kg）引起单相发热。对于稍高剂量（10¹·⁵ μg/kg），小鼠表现为双相发热。对于更高剂量（10¹·⁷⁵ - 10⁴ μg/kg），它们表现为多相发热，其中可识别出三个不同阶段。小鼠中LPS发热的剂量依赖性和动态似乎与大鼠中观察到的非常相似。然而，小鼠在低于热中性环境中对LPS的体温调节反应与大鼠明显不同。尽管非常高剂量（≥10⁴ μg/kg）确实在小鼠中引起了晚期（潜伏期约3小时）体温过低反应，但大鼠中典型的早期（潜伏期10 - 30分钟）体温过低反应并未出现。本研究确定了研究小鼠中LPS诱导的单相、双相和多相发热以及晚期体温过低的实验条件，并提供了这些反应的详细特征。
