Nervous and immune systems signals and connections: cytokines in hippocampus physiology and pathology

Signaling through secretion of small molecules is a hallmark of both nervous and immune systems. The scope and influence of the intense message exchange between these two complex systems are only now becoming objects of scientific inquiry. Both neurotransmitters and cytokines affect their target cells through surface receptors and also by other molecular mechanisms. Cytokine receptors are present in neurons and glial cell populations in discrete brain regions. This review firstly focuses on the role of cytokines in hippocampal physiological processes, such as memory and learning, and secondly on the pathological involvement of cytokines in diseases like depression and epilepsy. Interleukin-1β is necessary for long-term potentiation (LTP) maintenance in the hippocampus. On the other hand, interleukin-6 has a negative regulatory role in long-term memory acquisition. Astrocyte-secreted tumor necrosis factor plays a role in synaptic strength by increasing surface translocation of glutamate AMPA receptors, and the chemokine CXCL12 can silence the tonic activity of Cajal-Retzius neurons in the hippocampus. Manifold increased concentrations of interleukin-10, interferon-γ, ICAM1, CCL2, and CCL4 are observed in the hippocampi of patients with temporal lobe epilepsy. A contemporary view of the role of cytokines as neuromodulators is emerging from studies in humans and manipulations of experimental animals. Despite the accumulating evidence of the role of cytokines on nervous system physiology and pathology, it is important not to exaggerate its relevance.