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The Journal of Neuroscience, May 15, 1999, 19(10):3791-3800
Nature of the Retrograde Signal from Injured Nerves that Induces
Interleukin-6 mRNA in Neurons
Patricia G.
Murphy1,
Lindsay S.
Borthwick1,
Robert S.
Johnston1,
George
Kuchel2, and
Peter M.
Richardson1
Divisions of 1 Neurosurgery and
2 Geriatrics, Montreal General Hospital and McGill
University, Montreal, Canada H3G 1A4
In previous studies, interleukin-6 was shown to be synthesized in
approximately one-third of lumbar dorsal root ganglion neurons during
the first week after nerve transection. In present studies, interleukin-6 mRNA was found to be induced also in axotomized facial
motor neurons and sympathetic neurons. The nature of the signal that
induces interleukin-6 mRNA in neurons after nerve injury was analyzed.
Blocking of retrograde axonal transport by injection of colchicine into
an otherwise normal nerve did not induce interleukin-6 mRNA in primary
sensory neurons, but injection of colchicine into the nerve stump
prevented induction of interleukin-6 mRNA by nerve transection.
Therefore, it was concluded that interleukin-6 is induced by an injury
factor arising from the nerve stump rather than by interruption of
normal retrograde trophic support from target tissues or distal nerve
segments. Next, injection into the nerve of a mast cell degranulating
agent was shown to stimulate interleukin-6 mRNA in sensory neurons and
systemic administration of mast cell stabilizing agents to mitigate the
induction of interleukin-6 mRNA in sensory neurons after nerve injury.
These data implicate mast cells as one possible source of the factors
that lead to induction of interleukin-6 mRNA after nerve injury.
In search of a possible function of inducible interelukin-6, neuronal
death after nerve transection was assessed in mice with null deletion
of the interleukin-6 gene. Retrograde death of neurons in the fifth
lumbar dorsal root ganglion was 45% greater in knockout than in
wild-type mice. Thus, endogenous interleukin-6 contributes to the
survival of axotomized neurons.
Key words:
axotomy; dorsal root ganglion; interleukin-6; mast cells; peripheral nerve injury; neuronal death
Copyright © 1999 Society for Neuroscience 0270-6474/99/19103791-10$05.00/0
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