Insomnia, immunity, and inflammation - Mats Lekander

Background
Sleep and immune function are related through temporally organized neuroimmune processes. Sleep involves dynamic shifts in immune balance, with relative Th1-skewed proinflammatory predominance in early sleep and Th2-associated responses later in the night. Experimental sleep restriction activates proinflammatory transcriptional pathways, and may shift inflammatory activity into the daytime. Insomnia disorder, affecting ~10% of adults, is conceptualized as a state of hyperarousal and may involve microstructural alterations such as REM sleep instability, with potential but non-explored perturbed sleep-dependent immune regulation.

Objective
To critically examine mechanistic links between insomnia, inflammatory signaling, and infection-relevant immune function, with attention to causal inference.

Methods
Narrative synthesis of recent meta-analyses, Mendelian randomization (MR) studies, experimental sleep manipulation research, and translational reviews focusing on inflammatory biomarkers, sleep microstructure, and infection-related outcomes.

Results
Meta-analyses indicate modest elevations of inflammatory markers such as CRP and IL-6 in insomnia. Experimental sleep restriction induces inflammatory genomic activation. Some viral challenge studies show increased susceptibility to infection with shorter sleep duration, and objectively verified, but not self-reported, short sleep attenuates antibody responses to vaccination. Inflammatory cytokines modulate sleep–wake circuitry, and IL-6 has been linked to changes consistent with the sickness behavior model. Importantly, substantial heterogeneity characterizes observational studies, and MR analyses do not consistently support a causal effect of genetically determined insomnia on systemic inflammation. Instead, inflammatory