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LYPOPOLYSACCHARIDE INJECTION PROVOKES SECRETION OF PROINFLAMMATORY MEDIATORS OF INTERVERTEBRAL DISC DEGENERATION: GP91.

Chahine, Nadeen1; Bloom, Ona1; Grande, Daniel1; Sherry, Barbara1; Levine, Mitchell2

Spine Journal Meeting Abstracts: October 2011 - Volume - Issue - [no page #]
GENERAL POSTERS
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1 Feinstein Institute for Medical Research, Manhasset, NY, US;2 North Shore LIJ Health System, Dept of Neurosurgery, Manahsset, NY, US

INTRODUCTION: We propose a new approach for inducing inflammation in an animal model of disc degeneration that is not initiated by physical destruction of the disc integrity. We hypothesize that injection of rat caudal discs with lipopolysaccaride (LPS), an endotoxin used in pre‐clinical models of inflammation, can induce secretion of a cascade of pro‐inflammatory mediators of IVD degeneration. LPS is administered with micro needles in order to limit the potential disruption of the disc by needle injection.

METHODS: A 33G needle was inserted into the NP space of rat caudal discs, and 2.5 ng of LPS were injected. Saline was injected into adjacent sham discs. After 1 or 7 days post injection, disc protein lysates were prepared and assayed for TNF‐a and IL1‐b by ELISA, and for HMGB1 and MIF by immunoblotting.

RESULTS: Injection of LPS into the NP disc space resulted in increased levels of proinflammatory cytokines TNF‐a and IL‐1b vs. sham 1 day post injection. Elevated levels of IL‐1b persisted 7 days post injection with LPS (˜10X increase over time). No significant temporal change in TNF‐a was seen. HMGB1 and MIF were detected in discs treated with LPS at 1 and 7 days post disc injection, at greater levels than in sham group.

DISCUSSION: In this study, we have measured the effect of LPS injection on IVD cytokine secretion in vivo. Our results indicate that LPS is a potent stimulator of IL‐1b, TNF‐a, HMGB and MIF secretion in the IVD. The significant temporal increase in IL‐1b levels between days 1 and 7 suggests that LPS may initiate the process of prolonged disc inflammation, a hallmark indicator of painful disc degeneration in humans. The ability of LPS injection into the disc to provoke secretion of multiple cytokines (TNF‐a, IL‐1b, HMGB‐1 and MIF) may provide an opportunity to study broad aspects of the physiological inflammatory process observed in degenerative disc disease.

© 2011 Lippincott Williams & Wilkins, Inc.