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Intervertebral Disc Cells Produce Interleukins Found in Patients with Back Pain

Zhang, Yejia MD, PhD; Chee, Ana PhD; Shi, Peng DDS, PhD; Adams, Sherrill L. PhD; Markova, Dessislava Z. PhD; Anderson, David Greg MD; Smith, Harvey E. MD; Deng, Youping PhD; Plastaras, Christopher T. MD; An, Howard S. MD

American Journal of Physical Medicine & Rehabilitation: June 2016 - Volume 95 - Issue 6 - p 407–415
doi: 10.1097/PHM.0000000000000399
Original Research Articles
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Objective To examine the link between cytokines in intervertebral disc (IVD) tissues and axial back pain.

Design In vitro study with human IVD cells cultured from cadaveric donors and annulus fibrosus (AF) tissues from patients.

Results Cultured nucleus pulposus (NP) and AF cells were stimulated with interleukin (IL)-1β. IL-8 and IL-7 gene expression was analyzed using real-time polymerase chain reaction. IL-8 protein was quantified by enzyme-linked immunosorbent assay. After IL-1β stimulation, IL-8 gene expression increased 26,541 fold in NP cells and 22,429 fold in AF cells, whereas protein released by the NP and AF cells increased 2,389- and 1,784-fold, respectively. IL-7 gene expression increased 3.3-fold in NP cells (P < 0.05).

Cytokine profiles in AF tissues collected from patients undergoing surgery for back pain (painful group) or scoliosis (controls) were compared by cytokine array. IL-8 protein in the AF tissues from patients with back pain was 1.81-fold of that in controls. IL-7 and IL-10 in AF tissues from the painful group were 6.87 and 4.63 times greater than the corresponding values in controls, respectively (P < 0.05).

Conclusion Inflammatory mediators found in AF tissues from patients with discogenic back pain are likely produced by IVD cells and may play a key role in back pain.

From the Departments of Physical Medicine & Rehabilitation (YZ, CTP) and Orthopedic Surgery (YZ, HES), Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Translational Musculoskeletal Research Center (TMRC), Philadelphia Veterans Affairs Medical Center, Philadelphia, Pennsylvania (YZ, HES); Department of Orthopedic Surgery, Rush University Medical Center, Chicago, Illinois (AC, PS, HSA); Department of Biochemistry, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (SLA); Department of Internal Medicine, Rush University Medical Center, Chicago, Illinois (YD); and Department of Orthopedic Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania (DZM, DGA).

All correspondence and requests for reprints should be addressed to: Yejia Zhang, MD, PhD, Translational Musculoskeletal Research Center (TMRC), Philadelphia Veterans Affairs Medical Center, and Department of Physical Medicine and Rehabilitation, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.

Yejia Zhang was supported by NICHD (K08 HD049598). This work was supported in part by a grant from the North American Spine Society (NASS) and Scott F. Nadler, DO Research Grant Award by the Physiatric Association of Spine, Sports and Occupational Rehabilitation (PASSOR). This work has been presented as a poster presentation at the 2014 Philadelphia Spine Research Society Meeting.

AC performed tissue culture studies, real-time PCR and ELISA; PS performed human tissue dissections; DM performed human cytokine array; DGA and CP provided tissues from surgery and clinical information; YD performed cytokine pathway array and related data analysis; YZ, DGA and HSA were responsible for the conception, design, and data interpretation, and for obtaining grant funding. All authors critically reviewed and approved the manuscript.

Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article.

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