Transgenic mice and cytokine actions in the brain: bridging the gap between structural and functional neuropathology.

Deciphering the neurobiological consequences of cerebral cytokine expression in vivo represents an important research objective which has implications for our understanding of the pathogenesis and treatment of many significant neurological disorders. In our own pursuit of this objective, studies by us have utilized a transgenic strategy employing the GFAP promoter to direct the chronic expression of the cytokines IL-3, IL-6, IFN-alpha or TNF-alpha to astrocytes in mice. Transgenic expression of each cytokine produces a unique spectrum of neuropathological and functional alterations, thereby directly implicating these mediators in the pathogenesis of CNS disease. Moreover, as exemplified here with the GFAP-IL6 transgenic mice, these models are valuable tools in which to perform multi-level analysis to link molecular and cellular alterations to specific electrophysiological, neuroendocrine and behavioral outcomes. Integrative studies such as described here in the GFAP-cytokine transgenic mice, are providing a more thorough understanding of the actions of cytokines in the CNS and bridge the gap between structural and functional neuropathology. Copyright 1998 Elsevier Science B.V. All rights reserved.