Transgenic mice expressing interleukin-6 (IL6) in the brain exhibit gliosis, spongiosis and neuronal loss. Based on previous findings, we hypothesized that IL6 could upregulate the prion protein (PrP) gene in the central nervous system (CNS) of these mice. Western and Northern blot analysis showed that PrP protein and mRNA levels were comparable to control levels. Furthermore, ultrastructural characterization revealed that spongiosis was actually located in astrocytes. These results indicate that IL6 does not upregulate the cerebral PrP expression in this animal model and that profound astrocytic alterations precipitate the neuronal degeneration observed. (C) 1997 Elsevier Science Ireland Ltd.