Attenuation of Inflammatory Events in Human Intervertebral Disc Cells with a Tumor Necrosis Factor Antagonist

Abstract

<p>Tumor necrosis factor alpha (TNF&alpha;) is a known mediator of inflammation and pain associated with radiculopathy and intervertebral disc (IVD) degeneration. Soluble TNF receptors (sTNFR) and their analogues are of interest for the clinical treatment of these IVD pathologies although information on the effects of sTNFR on human IVD cells remains unknown. The objective of this study was to investigate an ability for soluble TNF receptor type II (sTNFRII) to antagonize TNF&alpha; induced inflammatory events in primary human IVD cells in vitro. IVD cells were isolated from surgical tissues procured from 15 patients and cultured with or without 1.4 nM TNF&alpha; (25ng/ml). Treatment groups were co-incubated with varying doses of sTNFRII (12.5-100nM). Nitric oxide (NO), prostaglandin E2 (PGE2), and interleukin-6 (IL6) levels in media were quantified to characterize the inflammatory phenotype of the IVD cells. </p><p>Across all patients, TNF&alpha; induced large, statistically significant increases in NO, PGE2, and IL6 secretion from cells compared to controls (60, 112, and 4-fold increases, respectively; p < 0.0001). Coincubation of TNF&alpha; with nanomolar doses of sTNFRII significantly attenuated the secretion of NO and PGE2 in a dose-dependent manner, while IL6 levels were unchanged. Mean IC50 values for NO and PGE2 were found to be 35.1 nM and 20.5 nM, respectively. These results suggest this soluble TNF receptor to be a potent TNF antagonist with potential to attenuate inflammation in IVD pathology.</p>