Astrocyte activation is a ubiquitous hallmark of the damaged brain and
has been suggested to play an important regulatory role in the activa
tion, survival, and regeneration of adjacent neurons, microglia, and o
ligodendrocytes. Little is known, however, about the endogenous signal
s that lead to this activation of astrocytes. Here we examined the reg
ulation of interleukin 6 (IL6), a proinflammatory cytokine, its recept
ors, and the effects of IL6-deficiency in a model of traumatic central
nervous system injury in the axotomized mouse facial motor nucleus. F
acial nerve transection led to a massive but transient upregulation of
IL6 mRNA in the disconnected motor nucleus, while IL6-receptor subuni
ts were constitutively expressed on motoneurons and astrocytes. Absenc
e of IL6 in genetically IL6-deficient mice led to massive reduction in
the number of activated GFAP-positive astrocytes, a more moderate dec
rease in microglial activation and proliferation, and an increase in t
he late neuronal response to axotomy. These results emphasize the role
of ILG in the global regulation of neurons, astrocytes, and microglia
and their activation in the injured nervous system. (C) 1997 Wiley-Li
ss, Inc.