Cytokines and sleep - still an unclear relationship.

Wakefulness and sleep-wake-regulation are complex states, a lot of different components and regulatory mechanisms contribute to these functions. One of the factors involved in sleep wake regulation is the immune system, itself being highly complex, consisting of humoral and cellular components. Molecules that transport the information are, beside others, the “immunotransmitters”, the cytokines. Psychoneuroimmunology – the relationship between psychic processes, neuronal function and the immune system – is a young field of research and related to both, „normal“ psychic function and psychiatric disorders such as major depression or schizophrenia. The evidence for a role of the immune system in sleep and sleep disorders is mainly based on two facts which are well known since many years: The sedation and fatigue inducing effect of proinflammatory cytokines such as Interleukin-1 (IL-1), Interleukin-6 (IL-6) or Tumor-necrose-factor-alpha (TNF-α) is well described by the model of “sickness behaviour” by the group of Robert Dantzer (Dantzer et al. 2008) and the extremely strong association between narcolepsy and the HLA-system (Fontana et al. 2010) Weschenfelder and colleagues wrote for this issue of ‘Psychiatria Danubina’ a comprehensive overview on the current state of knowledge in wakefulness and the definition of different terms and theoretical constructs involved in wakefulness. They describe the heterogeneity of the terminology and the differentiation between subjective and objective categories in sleep wake regulation. The description in part reflects the dilemma of the field: accepted definitions and objective criteria for the different stages are lacking. The current state of knowledge regarding the influence of cytokines on the regulation of wakefulness is modest until today. While the sleep inducing effect of cytokines was often described, regulatory effects of cytokines on the “normal” sleep wake regulation and on wakefulness are post-hoc conclusions from sickness models. TNF-α and IL-6, key-cytokines of the pro-inflammatory immuneresponse, are involved in different functions and diseases, e.g. they play a role in sleep apnoea and respond to sleep deprivation (Kapsimalis et al. 2008).