Attenuation of inflammatory events in human intervertebral disc cells with a tumor necrosis factor antagonist.
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2011-07
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Abstract
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The inflammatory responses of primary human intervertebral disc (IVD) cells to tumor necrosis factor α (TNF-α) and an antagonist were evaluated in vitro.Objective
To investigate an ability for soluble TNF receptor type II (sTNFRII) to antagonize TNF-α-induced inflammatory events in primary human IVD cells in vitro.Summary of background data
TNF-α is a known mediator of inflammation and pain associated with radiculopathy and IVD degeneration. sTNFRs 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 nmol/L TNF-α (25 ng/mL). Treatment groups were coincubated with varying doses of sTNFRII (12.5-100 nmol/L). 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, TNF-α induced large, statistically significant increases in NO, PGE₂, and IL6 secretion from IVD cells compared with controls (60-, 112-, and 4-fold increases, respectively; P < 0.0001). Coincubation of TNF-α with nanomolar doses of sTNFRII significantly attenuated the secretion of NO and PGE₂ in a dose-dependent manner, whereas IL6 levels were unchanged. Mean IC₅₀ values for NO and PGE₂ were found to be 35.1 and 20.5 nmol/L, respectively.Conclusion
Nanomolar concentrations of sTNFRII were able to significantly attenuate the effects of TNF-α on primary human IVD cells in vitro. These results suggest this sTNFR to be a potent TNF antagonist with potential to attenuate inflammation in IVD pathology.Type
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Sinclair, S Michael, Mohammed F Shamji, Jun Chen, Liufang Jing, William J Richardson, Christopher R Brown, Robert D Fitch, Lori A Setton, et al. (2011). Attenuation of inflammatory events in human intervertebral disc cells with a tumor necrosis factor antagonist. Spine, 36(15). pp. 1190–1196. 10.1097/brs.0b013e3181ebdb43 Retrieved from https://hdl.handle.net/10161/31400.
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Christopher Robert Brown
As an orthopaedic specialist and spine surgeon, I am committed to providing the best possible outcome for my patients with the least invasive surgery possible. I treat patients using the latest minimally invasive surgical techniques. Among the conditions I see in my patients are cervical radiculopathy and myelopathy, and traumatic spine injuries. Among the procedures I perform are complex cervical reconstruction, disc replacement surgery, minimally invasive scoliosis surgery, motion preservation spine surgery, and metastatic and tumor surgery.
Robert Douglas Fitch
My research interest center around limb lengthening and external fixation. Much is known about the biology of distraction osteogenesis. However, little is known about the effects on the soft tissues with limb lengthening techniques. In a dog model, we are investigating the effects of limb lengthening on muscle function, analizing amount of muscle lengthened per segment of bone lengthening, contractility, and strength. We also hope to begin studies assessing the effects of non steroidal anti-inflammatories on the quality of bone regenerate formed with distraction osteogenesis.
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