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

Purpose: 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.