Interleukin 18 and the brain: neuronal functions, neuronal survival and psycho-neuro-immunology during stress

Interleukin 18 (IL-18) is a pleiotropic cytokine that regulates peripheral innate and adaptive immune response and is also expressed in the brain. Here, we summarize the current knowledge on the biology of IL-18 in the brain and the efforts to determine its significance concerning neurological and psychiatric conditions. The picture that emerges is that of a heavily regulated molecule that can contribute to neuroinflammatory-mediated neuronal survival but can also serve as a neuromodulator that affects behaviour. We also summarize evidence showing how the brain can control the synthesis of peripheral IL-18 during stress by hormonal and neuronal signalling, regulating tissue-specific promoter usage. We discuss how this may represent one of the mechanisms by which the brain affects immune functions and what its implications are when considering IL-18 as a biomarker of psychiatric conditions.