INDUCTION OF INTERLEUKIN-6 IN AXOTOMIZED SENSORY NEURONS

RNA from rat dorsal root ganglia was analyzed in search of potentially beneficial cytokines that are induced in dorsal root ganglia by nerve injury. By reverse transcription, the PCR, and Southern blotting, int erleukin-6 mRNA was detected during development but not in normal adul t dorsal root ganglia, reappeared within 1 d of sciatic nerve transect ion, was maximally increased after 2 and 4 d, and decreased below the threshold of detection within 1 week. By RNase protection assay, inter leukin-6 mRNA was consistently present in RNA from dorsal root ganglia removed from rats 4 d following transection but not in control dorsal root ganglia. Interleukin-6 bioactivity was also present in dorsal ro ot ganglia following nerve injury. By in situ hybridization, interleuk in-6 mRNA was localized within large and medium-sized axotomized neuro ns. In summary, some sensory neurons respond to axotomy with a brisk t ransient increase in synthesis of interleukin-6. Injury to the sciatic nerve also induced mRNAs for interleukin-1 beta and tumor necrosis fa ctor-alpha, in dorsal root ganglia. The inductions of interleukin-1 be ta and tumor necrosis factor-alpha mRNAs were later and more sustained than that of interleukin-6 mRNA. The cellular sources of these two cy tokines have not been defined.