Disc related cytokines inhibit axonal outgrowth from dorsal root ganglion cells in vitro.
METHODS
Application of nucleus pulposus and disc related cytokines in vitro on cultured dorsal root ganglion (DRG) cells.


OBJECTIVE
To study if tumor necrosis factor (TNF) and interleukin-1beta (IL-1beta) may induce similar inhibition of axonal outgrowth from cultured DRG cells as application of nucleus pulposus and to compare a new assessment method to previous data.


BACKGROUND
Pro-inflammatory cytokines related to the intervertebral disc have been suggested to affect adversely neurons following local application, with implications for the nucleus pulposus-induced nerve injury seen in various studies. Nucleus pulposus is known to inhibit axonal outgrowth from cultured DRG cells, thereby indicating a neurotoxic potential. The mechanisms were not understood, but it was suspected that the effect was mediated by pro-inflammatory cytokines produced by the nucleus pulposus.


METHODS
DRG were harvested from newborn rats and put in culture. The axonal outgrowth was determined 24 hours after starting the culture. Twenty-four hours after exposing the cultured cells to nucleus pulposus, frozen nucleus pulposus, TNF, or IL-1beta, the axonal outgrowth was reassessed, and the outgrowth during the exposure time was calculated.


RESULTS
Nucleus pulposus clearly reduced the axonal outgrowth. Also, application of TNF and IL-1beta reduced the outgrowth but not as pronounced as the nucleus pulposus. Frozen nucleus pulposus had no effects on the outgrowth. Overall, the data were similar regarding frozen and nonfrozen nucleus pulposus compared to a previous study.


CONCLUSIONS
It was evident that the 2 studied cytokines inhibited the outgrowth of axons from cultured DRG cells, thus suggesting a neurotoxic potential. However, the inhibition was not as pronounced as for nucleus pulposus. These data may increase our understanding for cytokine induced nerve injury, with implications for future treatment strategies for such conditions.
Larsson
Karin
K
Department of Orthopaedics, Goteborg University, Sahlgrenska University Hospital, Gothenburg, Sweden.
Rydevik
Björn
B
Olmarker
Kjell
K
D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D015925:Cryopreservation; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000254:growth & development; D007375:Interleukin-1 / Q000378:metabolism / Q000494:pharmacology*; D007403:Intervertebral Disc / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology*
D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha