Interleukin-2 and the Septohippocampal System: An Update on Intrinsic Actions and Autoimmune Processes Relevant to...

Recent research suggests that lymphocytes can secrete classic neuropeptides, whereas peripheral immunization may signal hypothalamic neuronal cells. These results have led to more analysis of the function of cytokines as modulators of the peripheral and central nervous systems. In the past, the role of brain cytokines was thought to be a mere redundancy of their activity within the peripheral immune system. Nevertheless, it is currently appreciated that central nervous system (CNS) cytokines have selective effects on neuronal cells. Furthermore, recent research has revealed the involvement of various cytokines in the pathophysiologic processes of neurologic and neuropsychiatric diseases. Yet, despite a plethora of published literature, most of this clinical knowledge remains correlative, and much of the basic research has understandably relied on in vitro experimental designs. However, animal knockout models have provided valuable insight into the complex biology of cytokines, mainly of interleukin-2 (IL-2). Indeed, research has tried to unveil the effects of IL-2 on the septohippocampal system and its associated pathways that regulate learning, memory, and other processes. In this chapter, we provide a comprehensive summary of the studies investigating the role of intrinsic and extrinsic IL-2 in the CNS, particularly at the level of the septohippocampal system. We also discuss the function of other cytokines in this system and propose possible clinical correlates.