Lawther Adam J, Phillips Andrew J K, Chung Ni-Chun, Chang Aeson, Ziegler Alexandra I, Debs Sophie, Sloan Erica K, Walker Adam K
Laboratory of ImmunoPsychiatry, Neuroscience Research Australia, Randwick, New South Wales, 2031, Australia.
Turner Institute for Brain and Mental Health, School of Psychological Sciences, Monash University, Clayton, VIC, 3800, Australia.
Brain Behav Immun Health. 2022 Feb 8;21:100428. doi: 10.1016/j.bbih.2022.100428. eCollection 2022 May.
Disruption of circadian rhythms occurs in rotating shift-work, jetlag, and in individuals with irregular sleep schedules. Circadian disruption is known to alter inflammatory responses and impair immune function. However, there is limited understanding of how circadian disruption modulates cancer-induced inflammation. Inflammation is a hallmark of cancer and is linked to worse prognosis and impaired brain function in cancer patients. Here, we investigated the effect of circadian disruption on cancer-induced inflammation in an orthotopic breast cancer model. Using a validated chronic jetlag protocol that advances the light-cycle by 8 h every 2 days to disrupt circadian rhythms, we found that circadian disruption alters cancer-induced inflammation in a tissue-specific manner, increasing inflammation in the body and brain while decreasing inflammation within the tumor tissue. Circadian disruption did not affect inflammation in mice without tumors, suggesting that the impact of circadian disruption may be particularly detrimental in the context of underlying inflammatory conditions, such as cancer. Importantly, circadian disruption did not affect tumor burden, suggesting that increased inflammation was not a result of increased cancer progression. Overall, these findings identify the importance of healthy circadian rhythms for limiting cancer-induced inflammation.
昼夜节律的紊乱发生在轮班工作、时差反应以及睡眠时间表不规律的个体中。已知昼夜节律紊乱会改变炎症反应并损害免疫功能。然而，对于昼夜节律紊乱如何调节癌症诱导的炎症，人们了解有限。炎症是癌症的一个标志，与癌症患者的预后较差和脑功能受损有关。在这里，我们在原位乳腺癌模型中研究了昼夜节律紊乱对癌症诱导炎症的影响。使用经过验证的慢性时差方案，每2天将光周期提前8小时以扰乱昼夜节律，我们发现昼夜节律紊乱以组织特异性方式改变癌症诱导的炎症，增加身体和大脑中的炎症，同时减少肿瘤组织内的炎症。昼夜节律紊乱对没有肿瘤的小鼠的炎症没有影响，这表明昼夜节律紊乱的影响在潜在炎症条件（如癌症）的背景下可能特别有害。重要的是，昼夜节律紊乱不影响肿瘤负担，这表明炎症增加不是癌症进展增加的结果。总体而言，这些发现确定了健康的昼夜节律对于限制癌症诱导炎症的重要性。
