Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA, USA; Division of Sleep Medicine, Harvard Medical School, Boston, MA, USA.
Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Department of Surgery, University of California San Diego, San Diego, CA, USA.
Brain Behav Immun. 2024 Oct;121:142-154. doi: 10.1016/j.bbi.2024.07.023. Epub 2024 Jul 21.
Sleep deficiencies, such as manifested in short sleep duration or insomnia symptoms, are known to increase the risk for multiple disease conditions involving immunopathology. Inflammation is hypothesized to be a mechanism through which deficient sleep acts as a risk factor for these conditions. Thus, one potential way to mitigate negative health consequences associated with deficient sleep is to target inflammation. Few interventional sleep studies investigated whether improving sleep affects inflammatory processes, but results suggest that complementary approaches may be necessary to target inflammation associated with sleep deficiencies. We investigated whether targeting inflammation through low-dose acetylsalicylic acid (ASA, i.e., aspirin) is able to blunt the inflammatory response to experimental sleep restriction.
46 healthy participants (19F/27M, age range 19-63 years) were studied in a double-blind randomized placebo-controlled crossover trial with three protocols each consisting of a 14-day at-home monitoring phase followed by an 11-day (10-night) in-laboratory stay (sleep restriction/ASA, sleep restriction/placebo, control sleep/placebo). In the sleep restriction/ASA condition, participants took low-dose ASA (81 mg/day) daily in the evening (22:00) during the at-home phase and the subsequent in-laboratory stay. In the sleep restriction/placebo and control sleep/placebo conditions, participants took placebo daily. Each in-laboratory stay started with 2 nights with a sleep opportunity of 8 h/night (23:00-07:00) for adaptation and baseline measurements. Under the two sleep restriction conditions, participants were exposed to 5 nights of sleep restricted to a sleep opportunity of 4 h/night (03:00-07:00) followed by 3 nights of recovery sleep with a sleep opportunity of 8 h/night. Under the control sleep condition, participants had a sleep opportunity of 8 h/night throughout the in-laboratory stay. During each in-laboratory stay, participants had 3 days of intensive monitoring (at baseline, 5th day of sleep restriction/control sleep, and 2nd day of recovery sleep). Variables, including pro-inflammatory immune cell function, C-reactive protein (CRP), and actigraphy-estimated measures of sleep, were analyzed using generalized linear mixed models.
Low-dose ASA administration reduced the interleukin (IL)-6 expression in LPS-stimulated monocytes (p<0.05 for condition*day) and reduced serum CRP levels (p<0.01 for condition) after 5 nights of sleep restriction compared to placebo administration in the sleep restriction condition. Low-dose ASA also reduced the amount of cyclooxygenase (COX)-1/COX-2 double positive cells among LPS-stimulated monocytes after 2 nights of recovery sleep following 5 nights of sleep restriction compared to placebo (p<0.05 for condition). Low-dose ASA further decreased wake after sleep onset (WASO) and increased sleep efficiency (SE) during the first 2 nights of recovery sleep (p<0.001 for condition and condition*day). Baseline comparisons revealed no differences between conditions for all of the investigated variables (p>0.05 for condition).
This study shows that inflammatory responses to sleep restriction can be reduced by preemptive administration of low-dose ASA. This finding may open new therapeutic approaches to prevent or control inflammation and its consequences in those experiencing sleep deficiencies.
ClinicalTrials.gov NCT03377543.
睡眠不足，如表现为睡眠时间短或失眠症状，已知会增加涉及免疫病理学的多种疾病的风险。炎症被假设是睡眠不足作为这些疾病风险因素的作用机制之一。因此，减轻与睡眠不足相关的负面健康后果的一种潜在方法是针对炎症。很少有干预性睡眠研究调查了改善睡眠是否会影响炎症过程，但结果表明，可能需要采取补充方法来针对与睡眠不足相关的炎症。我们研究了通过低剂量乙酰水杨酸（ASA，即阿司匹林）靶向炎症是否能够抑制实验性睡眠限制的炎症反应。
46 名健康参与者（19 名女性/27 名男性，年龄范围 19-63 岁）在一项双盲随机安慰剂对照交叉试验中进行了研究，该试验有三个方案，每个方案包括为期 14 天的家庭监测阶段和为期 11 天（10 晚）的实验室入住阶段（睡眠限制/ASA、睡眠限制/安慰剂、对照睡眠/安慰剂）。在睡眠限制/ASA 条件下，参与者在家庭阶段和随后的实验室入住期间每晚晚上（22:00）服用低剂量 ASA（81mg/天）。在睡眠限制/安慰剂和对照睡眠/安慰剂条件下，参与者每天服用安慰剂。每个实验室入住阶段开始时，有 2 个晚上有 8 小时的睡眠机会（23:00-07:00）用于适应和基线测量。在两个睡眠限制条件下，参与者经历了 5 个晚上的睡眠限制，每个晚上只有 4 小时的睡眠机会（03:00-07:00），然后是 3 个晚上的恢复睡眠，有 8 小时的睡眠机会。在对照睡眠条件下，参与者在整个实验室入住期间有 8 小时的睡眠机会。在每个实验室入住期间，参与者进行了 3 天的密集监测（在基线、睡眠限制/对照睡眠的第 5 天和恢复睡眠的第 2 天）。使用广义线性混合模型分析包括促炎免疫细胞功能、C 反应蛋白（CRP）和活动记录仪估计的睡眠变量。
与安慰剂给药相比，低剂量 ASA 给药降低了 LPS 刺激的单核细胞中白细胞介素（IL）-6 的表达（条件天的 p<0.05），并降低了睡眠限制后 5 晚的血清 CRP 水平（条件的 p<0.01）。与安慰剂相比，低剂量 ASA 还降低了 LPS 刺激的单核细胞中 COX-1/COX-2 双阳性细胞的数量，在睡眠限制后 5 晚的恢复睡眠的第 2 晚（条件的 p<0.05）。与安慰剂相比，低剂量 ASA 进一步减少了恢复睡眠的前 2 晚的睡眠后觉醒（WASO）并增加了睡眠效率（SE）（条件和条件天的 p<0.001）。基线比较显示，所有研究变量在条件之间均无差异（条件的 p>0.05）。
这项研究表明，睡眠限制的炎症反应可以通过预先给予低剂量 ASA 来减轻。这一发现可能为预防或控制睡眠不足人群的炎症及其后果开辟新的治疗方法。
ClinicalTrials.gov NCT03377543。
