Universidad Nacional de Quilmes/CONICET, Buenos Aires, Argentina.
Chronobiol Int. 2009 Oct;26(7):1430-42. doi: 10.3109/07420520903408358.
Many immune parameters exhibit daily and circadian oscillations, including the number of circulating cells and levels of cytokines in the blood. Mice also have a differential susceptibility to lipopolysaccharide (LPS or endotoxin)-induced endotoxic shock, depending on the administration time in the 24 h light-dark (LD) cycle. We replicated these results in LD, but we did not find temporal differences in LPS-induced mortality in constant darkness (DD). Animals challenged with LPS showed only transient effects on their wheel locomotor activity rhythm without modification of circadian period and phase. Levels of several key factors involved in the pathology of sepsis and septic shock were tested in LD. We found that LPS-induced levels of interleukin (IL)-1beta, IL-6, JE (MCP-1), and MIP1alpha were significantly higher at zeitgeber time (ZT) 11 (time of increased mortality) than at ZT19 (ZT12 = time of lights-off in the animal quarters for the 12L:12D condition). Our results indicate that the differences found in mortality that are dependent on the time of LPS-challenge are not directly related to an endogenous circadian clock, and that some relevant immune factors in the development of sepsis are highly induced at ZT11, the time of higher LPS-induced mortality, compared to ZT19.
许多免疫参数表现出昼夜节律性波动，包括循环细胞数量和血液中细胞因子水平。小鼠对脂多糖（LPS 或内毒素）诱导的内毒素性休克的敏感性也存在差异，这取决于在 24 小时明暗（LD）周期中的给药时间。我们在 LD 中复制了这些结果，但在持续黑暗（DD）中没有发现 LPS 诱导的死亡率的时间差异。用 LPS 挑战的动物仅表现出对其轮式运动活动节律的短暂影响，而没有改变昼夜节律周期和相位。在 LD 中测试了参与败血症和感染性休克病理的几个关键因素的水平。我们发现，在 Zeitgeber 时间（ZT）11（死亡率增加的时间）时，LPS 诱导的白细胞介素（IL）-1β、IL-6、JE（MCP-1）和 MIP1α水平明显高于 ZT19（ZT12 =动物宿舍的熄灯时间对于 12L:12D 条件）。我们的结果表明，依赖于 LPS 挑战时间的死亡率差异与内源性昼夜节律钟无关，并且在败血症发展过程中的一些相关免疫因素在 ZT11 时被高度诱导，此时 LPS 诱导的死亡率较高，而在 ZT19 时则较低。
