The impact of microglia-derived cytokines upon gliosis in the CNS

Abstract

Injury to the CNS elicits a complex cellular response involving both astrocytes and microglia. Reactive glial populations make up the so-called 'glial scar' that has long been implicated as a barrier to axonal regeneration or as a causal factor in the genesis of epilepsy. Using in vitro models involving highly enriched populations of brain cells we have observed that astroglial growth is regulated in part by an immunomodulatory growth factor, or cytokine, called interleukin-1 (IL-1). A second cytokine, granulocyte-macrophage colony-stimulating factor (GM-CSF) serves as a potent microglial mitogen and regulator of the microglial component of the glial scar. Employing cytokines as tools to manipulate reactive gliosis, we found that IL-1 supported neuronal growth by action upon astroglia, while GM-CSF initiated epileptic-like discharges through mechanisms involving reactive microglia. We propose that a 'cytokine network' involving IL-1 and GM-CSF mediates the composition of glial scars at sites of CNS injury; these reactive glia, in turn, influence the survival and function of neighboring neurons.