THE IMPACT OF MICROGLIA-DERIVED CYTOKINES UPON GLIOSIS IN THE CNS

Injury to the CNS elicits a complex cellular response involving both a strocytes and microglia. Reactive glial populations make up the so-cal led 'glial scar' that has long been implicated as a barrier to axonal regeneration or as a causal factor in the genesis of epilepsy. Using i n vitro models involving highly enriched populations of brain cells we have observed that astroglial growth is regulated in part by an immun omodulatory 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 micro glial component of the glial scar. Employing cytokines as tools to man ipulate reactive gliosis, we found that IL-1 supported neuronal growth by action upon astroglia, while GM-CSF initiated epileptic-like disch arges through mechanisms involving reactive microglia. We propose that a 'cytokine network' involving IL-1 and GM-CSF mediates the compositi on of glial scars at sites of CNS injury; these reactive glia, in turn , influence the survival and function of neighboring neurons,