Studies on cytokine-induced sleep in prostanoid-related gene-manipulated mice

传染性疾病与睡眠时间的增加有关，并导致促炎细胞因子的产生和环氧化酶-2 （COX-2）的诱导，环氧化酶-2是前列腺素（pg）生物合成的关键酶。IL-1β和PGD_2均能促进大鼠和小鼠的睡眠。据报道，预处理COX-2抑制剂阻断了il -1β促进的大鼠睡眠。因此，PGs被认为介导了IL-1β在大鼠中的致睡作用。然而，对于PGs和细胞因子在小鼠睡眠觉醒调节中的分子相互作用知之甚少。在这里，我们使用PGD_2受体敲除小鼠和高选择性COX-2抑制剂NS-398来研究PGD2参与小鼠IL-1β的致睡作用。IL-1β增加了野生型和PGD_2受体敲除小鼠的非快速眼动（NREM）睡眠总量，并在晚上8点腹腔注射后6小时内降低了体温和运动活动。ns -398预处理既不能抑制WT小鼠自发性睡眠，也不能抑制il -1β诱导的睡眠。这些结果表明PGD_2不参与小鼠IL-1β的致睡作用。

Infectious illness is associated with an increase in the amount of sleep and causes the production of proinflammatory cytokines and induction of cyclooxygenase-2 (COX-2), which is the key enzyme of the biosynthesis of prostaglandins (PGs). Both IL-1β and PGD_2 promote sleep in rats and mice. Pretreatment of COX-2 inhibitor reportedly blocked the IL-1β-promoted sleep in rats. Therefore, PGs are considered to mediate the somnogenic effect of IL-1β in rats. However, little is known about the molecular interaction between PGs and cytokines in the sleep-wake regulation in mice. Here, we employed the PGD_2 receptor-knockout mice and highly selective COX-2 inhibitor NS-398 to examine the involvement of PGD2 in the somnogenic effect of IL-1β in mice. IL-1β increased total amount of non-rapid eye movement (NREM) sleep in both wild-type (WT) and PGD_2 receptor-knockout mice and concomitantly reduced body temperature and locomotor activity for 6h after the intraperitoneal injection at 8 p.m. Pretreatment ofNS-398 inhibited neither spontaneous nor IL-1β-induced sleep in WT mice. These results indicate that PGD_2 is not involved in the somnogenic effect of IL-1β in mice.