Circadian Misalignment and Inflammasome Dynamics: A Molecular Bridge Between Sleep and Inflammation

Sleep and inflammation are closely connected due to circadian regulation of immune pathways. The present review provides an overview of contemporary evidence on molecular interplay of sleep disruption and inflammasome upregulation, with consideration of NLRP3 as the primary complex. Attention was given to molecular mechanisms, including clock genes (BMAL1, CLOCK, PER, CRY), mitochondrial malfunction, as well as cytokine signaling. Articles were selected according to their relevance to inflammasome dynamics, neuroimmune modulation, and chronobiological manipulations. Circadian misalignment and sleep deprivation resulted in a uniform increase of NLRP3 inflammasome activation, interleukin-1 beta (IL-1β) and IL-18 secretion, and oxidative stress. Two important modulators of inflammatory priming are CRY inhibition and BMAL1 loss. Clinical associations include a higher risk of autoimmune, cardiometabolic, and neurodegenerative diseases in people who suffer from sleep disturbances frequently. Via circadian and mitochondrial processes, sleep disturbance is a potent modulator of systemic inflammation. Novel treatment options may be provided by modifying the inflammasome through lifestyle, melatonin, and chronotherapy. To comprehend the connection between inflammation and sleep, it becomes crucial to prioritize more mechanism-based research in the future.