Interleukin-6 contributes to initiation of neuronal regeneration program in the remote dorsal root ganglia neurons after sciatic nerve injury.

To assess the potential role of IL-6 in sciatic nerve injury-induced activation of a pro-regenerative state in remote dorsal root ganglia (DRG) neurons, we compared protein levels of SCG-10 and activated STAT3, as well as axon regeneration in IL-6 knockout (IL-6ko) mice and their wild-type (WT) counterparts. Unilateral sciatic nerve compression and transection upregulated SCG-10 protein levels and activated STAT3 in DRG neurons not only in lumbar but also in cervical segments of WT mice. A pro-regenerative state induced by prior sciatic nerve lesion in cervical DRG neurons of WT mice was also shown by testing for axon regeneration in crushed ulnar nerve. DRG neurons from IL-6ko mice also displayed bilaterally increased levels of SCG-10 and STAT3 in both lumbar and cervical segments after sciatic nerve lesions. However, levels of SCG-10 protein in lumbar and cervical DRG of IL-6ko mice were significantly lower than those of their WT counterparts. Sciatic nerve injury induced a lower level of SCG-10 in cervical DRG of IL-6ko than WT mice, and this correlates with significantly shorter regeneration of axons distal to the crushed ulnar nerve. These results suggest that IL-6 contributes, at the very least, to initiation of the neuronal regeneration program in remote DRG neurons after unilateral sciatic nerve injury.