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Attenuation of inflammatory events in human intervertebral disc cells with a tumor necrosis factor antagonist.

Publication ,  Journal Article
Sinclair, SM; Shamji, MF; Chen, J; Jing, L; Richardson, WJ; Brown, CR; Fitch, RD; Setton, LA
Published in: Spine (Phila Pa 1976)
July 1, 2011

STUDY DESIGN: 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.

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Published In

Spine (Phila Pa 1976)

DOI

EISSN

1528-1159

Publication Date

July 1, 2011

Volume

36

Issue

15

Start / End Page

1190 / 1196

Location

United States

Related Subject Headings

  • Young Adult
  • Tumor Necrosis Factor-alpha
  • Receptors, Tumor Necrosis Factor, Type II
  • Orthopedics
  • Nitric Oxide
  • Middle Aged
  • Intervertebral Disc Degeneration
  • Intervertebral Disc
  • Interleukin-6
  • Humans
 

Citation

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Sinclair, S. M., Shamji, M. F., Chen, J., Jing, L., Richardson, W. J., Brown, C. R., … Setton, L. A. (2011). Attenuation of inflammatory events in human intervertebral disc cells with a tumor necrosis factor antagonist. Spine (Phila Pa 1976), 36(15), 1190–1196. https://doi.org/10.1097/BRS.0b013e3181ebdb43
Sinclair, S Michael, Mohammed F. Shamji, Jun Chen, Liufang Jing, William J. Richardson, Christopher R. Brown, Robert D. Fitch, and Lori A. Setton. “Attenuation of inflammatory events in human intervertebral disc cells with a tumor necrosis factor antagonist.Spine (Phila Pa 1976) 36, no. 15 (July 1, 2011): 1190–96. https://doi.org/10.1097/BRS.0b013e3181ebdb43.
Sinclair SM, Shamji MF, Chen J, Jing L, Richardson WJ, Brown CR, et al. Attenuation of inflammatory events in human intervertebral disc cells with a tumor necrosis factor antagonist. Spine (Phila Pa 1976). 2011 Jul 1;36(15):1190–6.
Sinclair, S. Michael, et al. “Attenuation of inflammatory events in human intervertebral disc cells with a tumor necrosis factor antagonist.Spine (Phila Pa 1976), vol. 36, no. 15, July 2011, pp. 1190–96. Pubmed, doi:10.1097/BRS.0b013e3181ebdb43.
Sinclair SM, Shamji MF, Chen J, Jing L, Richardson WJ, Brown CR, Fitch RD, Setton LA. Attenuation of inflammatory events in human intervertebral disc cells with a tumor necrosis factor antagonist. Spine (Phila Pa 1976). 2011 Jul 1;36(15):1190–1196.

Published In

Spine (Phila Pa 1976)

DOI

EISSN

1528-1159

Publication Date

July 1, 2011

Volume

36

Issue

15

Start / End Page

1190 / 1196

Location

United States

Related Subject Headings

  • Young Adult
  • Tumor Necrosis Factor-alpha
  • Receptors, Tumor Necrosis Factor, Type II
  • Orthopedics
  • Nitric Oxide
  • Middle Aged
  • Intervertebral Disc Degeneration
  • Intervertebral Disc
  • Interleukin-6
  • Humans