Nature of the retrograde signal from injured nerves that induces interleukin-6 mRNA in neurons

In previous studies, interleukin-6 was shown to be synthesized in approxima tely 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 neuro ns. The nature of the signal that induces interleukin-6 mRNA in neurons aft er nerve injury was analyzed. Blocking of retrograde axonal transport by in jection of colchicine into an otherwise normal nerve did not induce interle ukin-6 mRNA in primary sensory neurons, but injection of colchicine into th e nerve stump prevented induction of interleukin-6 mRNA by nerve transectio n. Therefore, it was concluded that interleukin-6 is induced by an injury f actor arising from the nerve stump rather than by interruption of normal re trograde 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 cell s as one possible source of the factors that lead to induction of interleuk in-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 int erleukin-6 gene. Retrograde death of neurons in the fifth lumbar dorsal roo t ganglion was 45% greater in knockout than in wild-type mice. Thus, endoge nous interleukin-6 contributes to the survival of axotomized neurons.