Behavioral and Neurophysiological Effects of CNS Expression of Cytokines in Transgenic Mice

Numerous studies have documented the altered expression of various cytokines or their genes in the brain in a variety of central nervous system (CNS) pathologic states such as multiple sclerosis (MS), acquired immunodeficiency syndrome (AIDS) encephalopathy, stroke, Alzheimer’s disease, scrapie (spongiform encephalopathy), other infectious diseases and trauma. Whether the presence of cytokines in these neuropathologic states represents a primary or secondary event and the extent to which these factors may contribute to the development and progression of clinicopathologic alterations in these disorders remains largely unknown. We have focused on these issues by utilizing a transgenic approach to direct the constitutive expression of a variety of cytokines to astrocytes in the intact CNS of mice.1–4 Transgenic expression of cytokines in the CNS of mice allows not only the investigation of complex cellular responses at a localized level in the intact brain, but also more closely recapitulates the expression of these mediators as found in pathogenetic states.