The cytokine network and interleukin-15 (IL-15) in brain development

Cytokines are heterogeneous peptide molecules, produced by a variety of cells of immune and non-immune origin. Cytokines mediate a wide range of biological activities through a functional network, which they create. Cytokines utilise the complex receptor system, which includes a receptor subunit specific for each cytokine and common receptor subunits shared by cytokines which are members of the principal receptor family. After cytokine binding to a specific membrane receptor on target cells, a series of signal transduction pathways are stimulated. This may lead to translocation to the nucleus of phosphorylated signal transducers and activators of transcription (STAT) with up-regulation of the transcription and/or expression of new genes. Peripheral cytokines (e.g. interleukins) may enter the central nervous system in areas that lack a tight blood-brain barrier and/or by active transport. However, during systemic inflammation the brain is modulated not only by cytokines originated in peripheral organs but also by cytokines synthesised by the brain cells. Cytokines produced in the brain may influence its development, differentiation and function in normal and pathological circumstances. The recent description and characterisation of IL-15 indicate that this cytokine plays a pivotal role in inflammatory events. IL-15 binds to a receptor that possesses a unique alpha chain but utilises also the beta and gamma chains of the IL-2R to transduce signals in target T cells. In mast cells, IL-15 utilises a novel specific receptor IL-15RX. The IL-15 gene is constitutively expressed in the nerve tissue and during differentiation of neurons two distinct isoforms of IL-15 mRNA have been found. Results of our study provide the evidence that in the normal brain IL-15 is present only in neurons but glial cells contain this cytokine only when they are activated/transformed by inflammatory insults.