FEVER AND THERMOGENESIS IN RESPONSE TO BACTERIAL-ENDOTOXIN INVOLVE MACROPHAGE-DEPENDENT MECHANISMS IN RATS
FEVER AND THERMOGENESIS IN RESPONSE TO BACTERIAL-ENDOTOXIN INVOLVE MACROPHAGE-DEPENDENT MECHANISMS IN RATS
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DOI：
10.1152/ajpregu.1993.265.5.r1179
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发表时间：
1993-11-01
影响因子：
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通讯作者：
BERKENBOSCH, F
中科院分区：
文献类型：
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作者：
DERIJK, RH;STRIJBOS, PJLM;BERKENBOSCH, F
产热和体温升高（发热）通常伴随感染或损伤，并被认为是由内源性热原（例如细胞因子）介导的，这些热原是从活化的免疫细胞（如巨噬细胞）释放的。因此，我们研究了选择性消除外周巨噬细胞对耗氧量（VO 2）和结肠温度变化的影响，以响应细菌脂多糖（LPS）在大鼠。通过静脉注射含有药物二氯亚甲基二膦酸盐（Cl 2 MDP）的脂质体来消耗外周巨噬细胞。静息耗氧量和结肠温度不受巨噬细胞清除的影响。在完整大鼠中，外周注射LPS（0.1-0.5 mg/kg）引起结肠温度和氧消耗的增加，在较高剂量（2.5 mg/kg）下降低。消除大鼠外周巨噬细胞后，对LPS的致热和产热反应明显减弱。以前，我们已经报道，消除巨噬细胞钝化了血浆白细胞介素-1（IL-1）对LPS的反应。在这里，我们表明，消除巨噬细胞不影响血浆IL-6浓度的增加，在响应LPS。这些数据表明，致热和产热的反应，LPS至少部分依赖于涉及外周巨噬细胞的机制，外周产生的IL-1，而不是IL-6可能是一个重要的介体的变化，在耗氧量和结肠温度响应LPS。
Increases in thermogenesis and body temperature (fever) frequently accompany infection or injury and are thought to be mediated by endogenous pyrogens (e.g. cytokines), which are released from activated immune cells such as macrophages. Therefore, we have investigated the effect of selective elimination of peripheral macrophages on the changes in oxygen consumption (VO2) and colonic temperature in response to bacterial lipopolysaccharide (LPS) in the rat. Peripheral macrophages were depleted by intravenous injection of liposomes containing the drug dichloromethylene diphosphonate (Cl2MDP). Resting oxygen consumption and colonic temperatures were not affected by macrophage elimination. In intact rats, peripheral injection of LPS (0.1-0.5 mg/kg) elicited an increase in colonic temperature and in oxygen consumption that declined at higher doses (2.5 mg/kg). The pyrogenic and thermogenic responses to LPS were significantly attenuated in rats in which peripheral macrophages were eliminated. Previously, we have reported that elimination of macrophages blunts the plasma interleukin-1 (IL-1) response to LPS. Here we show that elimination of macrophages does not affect the increase in plasma IL-6 concentrations in response to LPS. These data indicate that the pyrogenic and thermogenic responses to LPS are at least in part dependent on mechanisms involving peripheral macrophages, and that peripherally produced IL-1 rather than IL-6 may be an important mediator of the changes in oxygen consumption and colonic temperature in response to LPS.