Romanovsky A A, Kulchitsky V A, Akulich N V, Koulchitsky S V, Simons C T, Sessler D I, Gourine V N
Thermoregulation Laboratory, Legacy Portland Hospitals, Oregon 97227, USA.
Am J Physiol. 1996 Jul;271(1 Pt 2):R244-53. doi: 10.1152/ajpregu.1996.271.1.R244.
We hypothesized that the systemic inflammatory response undergoes two consecutive stages, each characterized by different nonspecific sickness patterns. To test this hypothesis, we studied thermal, nociceptive, and motor responses to lipopolysaccharide (LPS) in 43 unanesthetized, habituated, and lightly restrained male Wistar rats previously implanted with a catheter in the jugular vein. Escherichia coli LPS was injected intravenously in a dose of 0, 0.1, 1, 10, 100, or 1,000 micrograms/kg. Colonic temperature (Tc) was measured with a thermocouple. Changes in nociception were assessed by tail flick latency (TFL) to a noxious heat stimulus. Motor activity was evaluated using an observation-based activity score (AS). The two lowest doses were apyrogenic. The next dose induced a monophasic fever with a maximal Tc rise of 0.9 +/- 0.2 degrees C at 108 +/- 11 min post-LPS. The next two higher doses caused biphasic fevers with the first and second peaks of 0.7 +/- 0.1 and 1.4 +/- 0.1 degrees C (10 micrograms/kg) and 0.7 +/- 0.1 and 1.4 +/- 0.2 degrees C (100 micrograms/kg) occurring at 60 +/- 6 and 165 +/- 17 min and at 45 +/- 3 and 141 +/- 6 min, respectively. The highest dose of LPS resulted in a Tc fall (nadir, -0.6 +/- 0.1 degree C at 83 +/- 6 min). Two different sickness patterns were exhibited. The first (high Tc, low TFL and high AS) occurred during the monophasic fever and the first (early) phase of the biphasic fevers, and it was termed the early phase syndrome. The second pattern (high or low Tc, high TFL, and low AS) developed during the second (late) phase of the biphasic fevers and LPS-hypothermia (endotoxin shock), and it was termed the late phase syndrome. Occurring at different stages of the systemic inflammatory response and developing through different coping patterns [fight/flight (energy expenditure) vs. depression/withdrawal (energy conservation)], the two syndromes represent two different types of adaptation to infection and have different biological significance. Viewing sickness as a dynamic entity is justified clinically. Such a dynamic approach to the problem resolves several contradictions in the current concept of sickness.
我们假设全身炎症反应经历两个连续阶段，每个阶段具有不同的非特异性疾病模式。为了验证这一假设，我们研究了43只预先在颈静脉植入导管的未麻醉、习惯化且轻度约束的雄性Wistar大鼠对脂多糖（LPS）的热、伤害性和运动反应。以0、0.1、1、10、100或1000微克/千克的剂量静脉注射大肠杆菌LPS。用热电偶测量结肠温度（Tc）。通过对有害热刺激的甩尾潜伏期（TFL）评估伤害感受的变化。使用基于观察的活动评分（AS）评估运动活动。最低的两个剂量无致热作用。下一个剂量诱导单相发热，LPS注射后108±11分钟时Tc最大升高0.9±0.2℃。接下来的两个更高剂量引起双相发热，10微克/千克组的第一和第二峰值分别为0.7±0.1和1.4±0.1℃，出现在60±6和165±17分钟；100微克/千克组的第一和第二峰值分别为0.7±0.1和1.4±0.2℃，出现在45±3和141±6分钟。最高剂量的LPS导致Tc下降（最低点，LPS注射后83±6分钟时为-0.6±0.1℃）。表现出两种不同的疾病模式。第一种（高Tc、低TFL和高AS）发生在单相发热和双相发热的第一（早期）阶段，被称为早期综合征。第二种模式（高或低Tc、高TFL和低AS）出现在双相发热的第二（晚期）阶段和LPS低温期（内毒素休克），被称为晚期综合征。这两种综合征发生在全身炎症反应的不同阶段，并通过不同的应对模式[战斗/逃跑（能量消耗）与抑郁/退缩（能量保存）]发展而来，代表了对感染的两种不同适应类型，具有不同的生物学意义。将疾病视为一个动态实体在临床上是合理的。这种对问题的动态方法解决了当前疾病概念中的几个矛盾。
