The effects of interferon-gamma on the central nervous system

Interferon-gamma (IFN-gamma) is a pleotropic cytokine released by T-lymphocytes and natural killer cells. Normally, these cells do not traverse the blood-brain barrier at appreciable levels and, as such, IFN-gamma is generally undetectable within the central nervous system (CNS). Nevertheless, in response to CNS infections, as well as during certain disorders in which the CNS is affected, T-cell traffic across the blood-brain barrier increases considerably, thereby exposing neuronal and glial cells to the potent effects of IFN-gamma. A larger portion of this article is devoted to the substantial circumstantial and experimental evidence that suggests that IFN-gamma plays an important role in the pathogenesis of the demyelinating disorder multiple sclerosis (MS) and its animal model experimental allergic encephalomyelitis (EAE). Moreover, the biochemical and physiological effects of IFN-gamma are discussed in the context of the potential consequences of such activities on the developing and mature nervous systems.