Interleukin-1α and tumor necrosis factor α as an inducer for reactive-oxygen-species-mediated NOD-like receptor protein 1/NOD-like receptor protein 3 inflammasome activation in mononuclear blood cells from individuals with chronic insomnia disorder.

BACKGROUND AND PURPOSE: There is some evidence that cytokines may play an important role in sleep deprivation; however, the underlying mechanisms are still unknown. So, the present study aimed to evaluate the relationship between NOD-like receptor protein 1 (NLRP1) and NOD-like receptor protein 3 (NLRP3) inflammasome activation of blood cells and serum levels of cytokines in individuals with chronic insomnia disorder (CID).

METHODS

Blood samples were collected from 24 individuals with CID and 24 healthy volunteers. The inflammasome activation was evaluated using real-time polymerase chain reaction of NLRP1, NLRP3, apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC) and caspase-1; western blot of NLRP1 and NLRP3; caspase-1 activity assay; and serum levels of interleukin-1β (IL-1β), IL-18 and other cytokines using enzyme-linked immunosorbent assay. Reactive oxygen species generation in blood cells were detected by flow cytometry assay. Also, magnetic resonance imaging scans were obtained on a Siemens Magnetom Avanto 1.5 T MRI whole-body scanner using an eight-channel head coil.

RESULTS

Increased activity of NLRP1 and NLRP3 inflammasomes in blood cells, increased serum levels of pro-inflammatory cytokines and decreased serum levels of IL-10 and transforming growth factor β in individuals with CID were found. Significant correlation was observed between increased serum concentration of IL-1β and the severity of insomnia in individuals with CID. The levels of reactive oxygen species in blood cells were found to be correlated with IL-1α and tumor necrosis factor α concentrations in sera from individuals with CID. Moreover, the individuals with CID demonstrated increased right cerebellum cortex and lateral ventricle mean diffusivity bilaterally compared to controls.

CONCLUSIONS

This study provided new insights on the pathogenesis of CID and the effects of cytokines on inflammasome activation.