Brain interleukin-1β expression and action in the absence of neuropathology
Résumé
The brain parenchyma has long been considered immunologically privileged based on the lack of a true lymphoid system. It is, however, clear now that brain infection or injury elicits innate immune responses including the release of cytokines, such as interleukin-1 beta(IL-1 beta). Interestingly, low levels of IL-1 beta are already present in the developing and adult brain in the absence of any infection or injury, indicating that this cytokine plays a role in the modulation of central nervous system functioning. The aim of this chapter is to provide some insight into the different roles IL-1 beta may play in the brain in the absence of neuropathology and to outline the difficulties and pitfalls associated with the study of brain IL-1 beta expression and action. Brain IL-1 beta expression during postnatal development has been hypothesized to regulate neuronal survival in a nerve growth factor (NGF)-dependent way. It is becoming clear that the constitutive low expression of IL-1 beta in the adult hippocampus plays a role in spatial learning and memory processes, possibly through its role in maintaining long-term potentiation. The circadian variation in expression of IL-1 beta in the adult forebrain is proposed to play a role in the physiological regulation of sleep, probably as a circulating factor in the cerebrospinal fluid. Constitutive IL-1 beta expression in neuroendocrine hypothalamic nuclei might act as a true neuropeptide and mediate neuroendocrine responses in response to physical stressors. The peripheral administration of bacterial lipopolysaccharides induces de novo IL-1 beta synthesis at the blood-brain interface without disrupting the blood-brain barrier. This transient IL-1 beta production at the blood-brain interface in response to peripheral immune stimuli is thought to constitute a signal mediating behavioral changes during infectious and inflammatory diseases. In conclusion, it is recognized increasingly that IL-1 beta production and action in the brain is involved in various neurobiological responses that are distinct from its classical role in mediating cellular responses to infection and injury.