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

Abstract

Study Design The inflammatory responses of primary human intervertebral disc (IVD) cells to tumor necrosis factor (TNFα) and an antagonist were evaluated in vitro. Objective To investigate an ability for soluble TNF receptor type II (sTNFRII) to antagonize tumor necrosis factor alpha (TNFα) induced inflammatory events in primary human IVD cells in vitro. Summary of Background Data TNFα is a known mediator of inflammation and pain associated with radiculopathy, and 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. Methods IVD cells were isolated from surgical tissues procured from 15 patients and cultured with or without 1.4 nM TNFα (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. Results Across all patients, TNFα induced large, statistically significant increases in NO, PGE2, and IL6 secretion from IVD cells compared to controls (60, 112, and 4-fold increases, respectively; p < 0.0001). Coincubation of TNFα 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. Conclusions Nanomolar concentrations of sTNFRII were able to significantly attenuate the effects of TNFα on primary human IVD cells in vitro. These results suggest this soluble TNF receptor to be a potent TNF antagonist with potential to attenuate inflammation in IVD pathology.

Cytokine inhibition and time-related influence of inflammatory stimuli on the hyperalgesia induced by the nucleus pulposus

“…Although cytokines were found in large quantities in herniated nucleus pulposus [26,27], it was unclear whether the cytokine secretion would be derived from inflammatory cells that infiltrated the herniated nucleus pulposus tissue or from disc-derived cells. The capacity of normal disc cells to secrete proinflammatory cytokines and interleukin-10 in the absence of inflammatory cells was observed in cultured murine disc [28]. TNF-a is spontaneously produced by intervertebral disc tissue in culture, and it has been found in the NP cells of rats and pigs [8,18,27].…”

Molecular Basis of Intervertebral Disc Degeneration and Herniations: What Are the Important Translational Questions?

“…This suggests that supplementing native IL-1 receptor antagonist molecules might help prevent or slow disc degeneration. Despite some in vitro evidence supporting both TNF-a inhibitors and IL-1 receptor antagonists, in vivo and clinical effectiveness still needs to be demonstrated for intervertebral disc degeneration [45,82].…”

Epigallocatechin 3-gallate suppresses interleukin-1β-induced inflammatory responses in intervertebral disc cells in vitro and reduces radiculopathic pain in rats

“…Recently, tissueengineered IVDs that formed a functional motion segment were used to replace the degenerated discs in rodent caudal spine (Bowles et al, 2011) and chemical crosslinking was applied to stabilise the AF tissue in vitro (Hedman et al, 2006). Anti-inflammatory and anti-catabolic substances that target the metabolism and inflammatory signalling within the IVD also represent a new, interesting treatment option (Klawitter et al, 2012a;Klawitter et al, 2012b;Sinclair et al, 2011;Wuertz et al, 2011).…”