Sleep quality refers to an individual's self-satisfaction with various aspects of the sleep experience, which includes four attributes: sleep efficiency, sleep latency, sleep duration, and wakefulness after falling asleep (Nelson et al., 2022). Genetics (Dashti et al., 2019), diet (Saidi et al., 2020), physical activity (Murawski et al., 2018) and environmental factors (Ageborg et al., 2018) are all influencing factors of sleep quality. Good sleep quality can reduce energy consumption, increase the recovery of energy stored in the brain, and participate in regulating adaptive and congenital immune response (Irwin, 2015; Hu et al., 2020). Sleep disorders, usually a manifestation of abnormal sleep quality and various abnormal behaviors during sleep, is also a manifestation of disturbances in the normal rhythmic altercations of sleep and wakefulness, including insomnia, daytime sleepiness, abnormal sleep behavior, obstructive sleep apnea, etc., currently affect nearly a quarter of the world's population (Rémi et al., 2019) and are most commonly associated with depression (Fang et al., 2019), which can have a serious impact on patients' mental health (Pavlova and Véonique, 2019). Impaired sleep is often observed as a major complaint in patients with depression (Armitage, 2007).

Over the past two decades, many studies have demonstrated that sleep disorders increase the risk of inflammatory diseases (Dew et al., 2003; Vgontzas et al., 2013). Some markers of systemic inflammation are associated with the pathophysiology of sleep disorders (Irwin et al., 2016). Sleep quality mainly affects the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS) (Irwin and Cole 2011), while activation of β-adrenergic signaling induces inflammatory gene expression, proinflammatory cytokine production, and an increase in systemic inflammatory markers (Irwin et al., 1999).

Recently, many inflammatory factors have been shown to affect sleep in laboratory animals and humans. Among them, the most widely studied sleep-regulating inflammatory factors are IL-1b, IL-6, and TNF-a (Veler, 2023). So far, the most significant changes in inflammatory factors found in poor sleep quality are: (1) the elevation of TNF-α (Atrooz and Samina, 2020; Zhai et al., 2021). (2) increased IL-1, Il-1β, IL-6, IL-8, IL-10, IL-17 (Atrooz and Samina, 2020; Zhai et al., al.,2021; Huang et al., 2019; Alqaderi et al., 2023). (3) increased CRP (Irwin et al., 2016). (4) increased NFkB (Atrooz and Samina, 2020). (5) The increase of VEGF (Alqaderi et al., 2023)

At present, there is growing evidence of an association between inflammatory factors and sleep, but the data provided by the literature is still insufficient and varied. And research on sleep has focused on obstructive sleep apnea (Wali et al., 2021), obesity (Huang et al., al.,2019), healthy people (Dzierzewski et al., 2020), schizophrenia (Lee et al., 2019), bipolar disorder (Lee et al., 2021), post-traumatic stress disorder (Yeh et al., 2023), pregnant women (Carroll et al., al.,2020), and so on. There are few studies on the relationship between inflammatory factors and sleep in Major depressive disorder (MDD) patients.

Therefore, the purpose of this study was to investigate the difference of peripheral blood inflammatory factors in MDD patients with or without sleep disorders, so as to explore sleep-related inflammatory factors in MDD patients. Based on the hypothesis of previous studies of depression-related inflammatory factors (Marini et al., 2016; Bengoechea-Fortes et al., 2023) and sleep-related inflammatory factors (Veler, 2023), we selected the following inflammatory factors: IL-1β, IL-2, IL-6, IL-8, IL-10, CRP, TNF-α, CXCL-1, CXCL-2, and IFN-γ. Our main research questions are: (1) What inflammatory factors are associated with sleep in MDD patients? (2) Is there a linear relationship between levels of inflammatory factors and sleep quality? (3) Which inflammatory factors can predict poorer sleep quality in MDD patients?