Complete loss of sleep can be lethal, but a mechanism for the lethality has heretofore proven elusive. In a recent work in Cell, Sang et al. present findings that suggest a mechanism whereby sleep loss causes systemic inflammation and multiple organ dysfunction; triggering the cytokine storm is a brain-derived chemical, prostaglandin D2, which is released via dynamic regulation of the blood brain barrier.

Sleep is a conserved behavior widely observed in animals ranging from humans to jellyfish.¹ The importance of sleep is underscored by the detrimental consequences of partial sleep loss on cognitive function, neural activity, immune system function, and metabolism. Strikingly, complete loss of sleep can be lethal in certain species. In 1983, Allan Rechschtaffen and colleagues reported that total sleep deprivation (TSD) is deadly to rats.² TSD results in a hypermetabolic state (exhibiting weight loss despite increased food intake), skin breakdown, multi-organ failure and, inevitably, death. These TSD experiments utilized a clever technique that the authors developed called “disc-over-water”. A rat is placed on a platform that rotates whenever the rat falls asleep, forcing the animal awake to avoid falling into water surrounding the platform. However, the mechanisms of this lethality have remained largely a mystery for 40 years.