Restricting sleep, either voluntarily or as response to work requirements, is increasing in all western societies. Homeostatic sleep regulation responds to this restriction by increasing the duration and depth of the sleep period that follows the prolonged wakefulness period. Occasional prolongation of wakefulness can be thus be compensated for. However, when sleep restriction becomes chronicle, several symptoms of restricted performance as well as health consequences start to appear.

Immune system is one of the first to react to prolonged wakefulness. Several components of the host defense reaction are activated, including the folded protein response, as indicated e.g. by increase in BiP expression, iNOS synthesis and in humans, by increase in c-reactive protein, CRP. In addition, several cytokines respond to sleep restriction. Interestingly, many cytokines are also sleep-inducing, giving an explanation to the well-known phenomenon that during infection both animals and humans increase sleep. If sleep restriction continues, the immune system starts to loose its effectiveness: e.g. wound healing is compromised and the ability of young volunteers with partial, chronicle sleep restriction produced less antibodies as response to influenza vaccination than those who had slept normally. In extreme cases (experiments done with rodents), lethal infection from normally non-pathogenic bacterial flora takes place.