Association of Complete Blood Count-Derived Inflammatory Markers with Trouble Sleeping: Evidence from Population Data and Experimental Sleep Deprivation

Chujun Duan,1,2 Yuan Zhang,2 Peng Fang,3 Ranran Wang,2 Yilin Wu,2 Yuling Wang,2 Hanyin Fan,2 Yangmengjie Jing,2 Linqi Feng,2 Jinyue Yang,2 Ran Zhuang1,2 1School of Life Science and Technology, Northwestern Polytechnical University, Xi’an, Shaanxi, People’s Republic of China; 2Department of Immunology, Fourth Military Medical University, Xi’an, Shaanxi, People’s Republic of China; 3Department of Military Medical Psychology, Military Medical Innovation Center, Fourth Military Medical University, Xi’an, Shaanxi, People’s Republic of ChinaCorrespondence: Ran Zhuang, Department of Immunology, Fourth Military Medical University, #169 Changle West Road, Xi’an, Shaanxi, 710032, People’s Republic of China, Email [email protected]: Trouble sleeping is a common pathophysiological feature underlying sleep disorders and affects both the number and function of immune cells. This study investigated the associations between complete blood count (CBC)-derived inflammatory markers and trouble sleeping, aiming to provide a simple and rapid reference for evaluating sleep-related conditions.Patients and methods: A total of 39,156 participants from the 2011– 2018 NHANES cycles were included. Survey-weighted multivariable logistic regression was performed to examine the associations between CBC-derived inflammatory markers and trouble sleeping. Restricted cubic spline models were applied to assess potential nonlinear relationships, and stratified analyses were conducted for robustness. Additionally, a human study in healthy volunteers evaluated the effects of short-term sleep deprivation (36 h) and subsequent recovery on CBC-derived inflammatory markers and circulating pro-inflammatory cytokines.Results: Participants with trouble sleeping had shorter sleep duration and elevated levels of several CBC-derived inflammatory markers compared with those without trouble sleeping. Sleep insufficiency was particularly associated with increased monocyte-to-lymphocyte ratio (MLR, p < 0.001). Besides, systemic inflammation response index (SIRI) emerged as an independent predictor of trouble sleeping [OR = 1.07 (95% CI: 1.02– 1.12), p = 0.008], particularly in adults aged 30– 60, males, non-Hispanic Whites, individuals with obesity, and those with higher education; this association persisted in never smokers and participants without major comorbidities. In the human experimental study, acute sleep deprivation markedly increased CBC-derived markers, which largely returned to baseline following recovery sleep. Regarding circulating cytokines, only IL-6 remained elevated despite recovery, highlighting its key role in the inflammatory response to sleep loss.Conclusion: The findings highlight the link between trouble sleeping and CBC-derived inflammatory markers, with SIRI emerging as a potential predictor of trouble sleeping and IL-6 as a key cytokine involved in the inflammatory response to sleep deprivation.Keywords: blood cell count, inflammation, cytokines, NHANES