IL-6 induces regionally specific neural injury in the spinal cord. (A) IL-6 was administered to cortical, hippocampal, and spinal cord organotypic cultures at increasing doses, and cell death was assessed 36 hours later. Data is plotted as the fold induction of death relative to cultures with no IL-6 addition. (B) Adult rats were infused with IL-6 or saline through an intracerebroventricular (IC) cannula at the same rate (0.5 μl/h for 7 days) and concentration (2,000 pg/ml) as that previously administered via a spinal subarachnoid catheter and assessed for weakness. (C) Cortical organotypic cultures were treated with IL-6 and assessed for PARP activity up to 20 hours later. (D) Confocal microscopy of cortex and spinal cord organotypic cultures was performed after the administration of IL-6 to the culture. Scale bars: 50 μm. (E) RT-PCR analysis of iNOS from cortex or spinal cord organotypic cultures was performed at various times after the addition of IL-6. GAPDH serves as a PCR control. (F) Quantitative immunoblot of IL-6R expression from human autopsy tissue lysates. Spinal cord grey and white matter (SCGM and SCWM, respectively) and cortex grey and white matter (CoWM and CoGM, respectively) lysates were generated, subjected to SDS-PAGE, and probed for IL-6R immunoreactivity. (G) Quantitative immunoblot of sIL-6R from the same lysates (shown in chemiluminescent units). (H) Adult rats were infused with either IL-6 or IL-6 plus sIL-6R at a 1:1 molar ratio through a spinal subarachnoid catheter as before. Animals were assessed for hind limb grip strength for the 10-day duration of the experiment. *P < 0.05; **P < 0.04.