Concluding Remarks

Inflammatory cytokines are of interest in the context of sleep and circadian rhythms for several reasons. These molecules usually operate on much longer timescales, i.e., minutes and hours, than those of classical neurotransmitters, and they concord with those of sleep switches and circadian rhythms. Proinflammatory cytokines are released during inflammation and infectious diseases, and are therefore suitable candidates for mediating alterations in sleep and circadian rhythms in these conditions. Furthermore, since therapies based on manipulations of the cytokine network are of current interest, the timing of drug administration in these therapies should be considered in order to minimize adverse effects on sleep and circadian rhythms. Considering the complexity of circadian rhythms and sleep regulation and the relationship between the two processes, a more detailed understanding of the roles and actions played by cytokines in these neural circuits is required. Thus, the cellular localization of cytokines and cytokine receptors in neural centers involved in these processes needs to be better mapped. Furthermore, the potential circadian variation in their expression, as well as in the intracellular systems regulating their responses in the nervous system, needs to be determined. Novel knowledge on how cytokines can regulate and dysregulate sleep and circadian rhythms is a main challenge for the near future.

Acknowledgment. This work was supported by EC grant LSHM-CT-518189.

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