Expression and Distribution of Tumor Necrosis Factor Alpha in Human Lumbar Intervertebral Discs: A Study in Surgical Specimen and Autopsy Controls

Weiler, Christoph; Nerlich, Andreas G.; Bachmeier, Beatrice E.; Boos, Norbert

doi:10.1097/01.brs.0000149186.63457.20

Cited by 296 publications

(273 citation statements)

References 60 publications

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“…Furthermore, the patients with lumbar radiculopathy caused by disk herniation were younger than those with cervical myelopathy. A previous cadaveric study demonstrated that the correlation between anular TNF-a and age was highly significant [29]. Therefore, there is a possibility that the differences in cytokines among the three groups were attributable to age.…”

Section: Discussionmentioning

confidence: 91%

Tumor necrosis factor-α, interleukin-1β, and interleukin-6 in the cerebrospinal fluid of patients with cervical myelopathy and lumbar radiculopathy

et al. 2009

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There have been few reports describing cytokines in the cerebrospinal fluid (CSF) of patients with spinal degenerative disorders. This study investigated whether interleukin-1b (IL-1b), interleukin-6 (IL-6), and tumor necrosis factor-a (TNF-a) could be detected in CSF of patients with cervical myelopathy or lumbar radiculopathy and whether the concentrations of those cytokines correlated with the severity of disease conditions. CSF samples were obtained from 21 patients with cervical myelopathy (Group M) and 19 patients with lumbar radiculopathy (Group R), and six volunteers (control). The concentration of IL-6 was significantly higher in Groups M and R than in the control, possibly demonstrating spinal cord and nerve root damage, respectively. However, TNF-a was lower than the detection limit. IL-1b was detected in only five samples from three patients in Group M and two volunteers in the control. The concentrations of IL-6 did not show any correlation with symptom duration, the scoring system by the Japanese Orthopaedic Association, or the duration of nerve root block. There is a possibility that the concentration of inflammatory cytokines in CSF can indicate certain pathological aspects of cervical myelopathy or lumbar radiculopathy.

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Section: Discussionmentioning

confidence: 91%

Tumor necrosis factor-α, interleukin-1β, and interleukin-6 in the cerebrospinal fluid of patients with cervical myelopathy and lumbar radiculopathy

et al. 2009

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“…In herniated disc, TNF-a is expressed at higher levels compared to asymptomatic or autopic controls [29]. Moreover, cytokines play a role in the generation of neuropathic pain both in the peripheral and central nervous systems [30][31][32] and participation of pro-inflammatory cytokines in the genesis of changes of nervous tissue and symptoms generated by lumbar disc herniation has been emphasized by several authors [32][33][34].…”

Section: Discussionmentioning

confidence: 99%

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

2011

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Introduction The symptoms of lumbar disc herniation, such as low back pain and sciatica, have been associated with local release of cytokines following the inflammatory process induced by the contact of the nucleus pulposus (NP) with the spinal nerve. Material and methods Using an animal experimental model of intervertebral disc herniation and behavioral tests to evaluate mechanical (electronic von Frey test) and thermal (Hargreaves Plantar test) hyperalgesia in the hind paw of rats submitted to the surgical model, this study aimed to detect in normal intervertebral disc the cytokines known to be involved in the mechanisms of inflammatory hyperalgesia, to observe if previous exposure of the intervertebral disc tissue to specific antibodies could affect the pain behavior (mechanical and thermal hyperalgesia) induced by the NP, and to observe the influence of the time of contact of the NP with the fifth lumbar dorsal root ganglion (L5-DRG) in the mechanical and thermal hyperalgesia. Results The cytokines present at highest concentrations in the rat NP were TNF-a, IL-1b and CINC-1. Rats submitted to the disc herniation experimental model, in which a NP from the sacrococcygeal region is deposited over the right L5-DRG, showed increased mechanical and thermal hyperalgesia that lasted at least 7 weeks. When the autologous NP was treated with antibodies against the three cytokines found at highest concentrations in the NP (TNF-a, IL-1b and CINC-1), there was decrease in both mechanical and thermal hyperalgesia in different time points, suggesting that each cytokine may be important for the hyperalgesia in different steps of the inflammatory process. The surgical remotion of the NP from herniated rats 1 week after the implantation reduced the hyperalgesia to the level similar to the control group. This reduction in the hyperalgesia was also observed in the group that had the NP removed 3 weeks after the implantation, although the intensity of the hyperalgesia did not decreased totally. The removal of the NP after 5 weeks did not changed the hyperalgesia observed in the hind paw, which suggests that the longer the contact of the NP with the DRG, the greater is the possibility of development of chronic pain. Conclusion Together our results indicate that specific cytokines released during the inflammatory process induced by the herniated intervertebral disc play fundamental role in the development of the two modalities of hyperalgesia (mechanical and thermal) and that the maintenance of this inflammation may be the most important point for the chronification of the pain.

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“…The local production of matrix-degrading enzymes is a key event leading to degeneration, but it must be also considered in the context of the upstream molecules, such as cytokines, which regulate enzyme synthesis. IVD cells have a capacity to express a range of cytokines [6,7], including pro-inflammatory molecules, such as both isoforms of interleukin-1, alpha (IL-1a) and beta (IL-1b) [8] and tumor necrosis factor alpha (TNF-a) [9]. It has been proposed that IL-1 can regulate IVD cell expression of key matrixdegrading enzymes in vitro [10] and in vivo [11], placing this cytokine as a main factor inducing degeneration.…”

Section: Introductionmentioning

confidence: 99%

Human mesenchymal stem cell co-culture modulates the immunological properties of human intervertebral disc tissue fragments in vitro

et al. 2010

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The capacity of mesenchymal stem cells (MSCs) to differentiate into intervertebral disc (IVD)-like cells has been well described, but their ability to modulate the inflammatory processes in the IVD remains unclear. We found that tissue obtained by discectomy of degenerated and post-traumatic IVD contains significant amounts of IgG antibodies, a sign of lymphocyte infiltration. Further we investigated whether MSCs in vitro, which were characterized for their multilineage differentiation potential and may have immunomodulatory effects on IVD fragments. IVD fragments were co-cultured in contact with peripheral blood lymphocytes (PBLs) and MSCs, and as functional controls we used contact co-cultures of PBLs stimulated with pokeweed mitogen (2.5 lg/mL) and MSCs. The time course of lymphocyte proliferation (Alamar Blue), IgG (ELISA) and gene expression (RT-PCR) of anti-inflammatory cytokines (TGF-b1, IL-10) by MSCs and proinflammatory molecules (IL-1a, IL-1b and TNF-a) by the IVD fragments were analyzed. Depending on the response to the presence of MSCs, the IVD fragments (n = 13) were divided in two groups: responders (n = 9), where inflammation was inhibited by MSCs and non-responders (n = 4), where MSCs did not decrease inflammation. At 1 week in co-culture, MSCs reduced significantly the IgG production in the IVD responders group to 69% and PBLs proliferation to 57% of the control. MSCs expression of the anti-inflammatory TGF-b1 increased with time, while IL-10 was expressed only at day 1. IVD gene expression of TNF-a decreased constantly, whereas IL-1a and IL-1b expression increased. In conclusion, these data suggest that MSCs may modulate disc-specific inflammatory and pain status and aid regeneration of the host tissue.

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Expression and Distribution of Tumor Necrosis Factor Alpha in Human Lumbar Intervertebral Discs: A Study in Surgical Specimen and Autopsy Controls

Cited by 296 publications

References 60 publications

Tumor necrosis factor-α, interleukin-1β, and interleukin-6 in the cerebrospinal fluid of patients with cervical myelopathy and lumbar radiculopathy

Tumor necrosis factor-α, interleukin-1β, and interleukin-6 in the cerebrospinal fluid of patients with cervical myelopathy and lumbar radiculopathy

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

Human mesenchymal stem cell co-culture modulates the immunological properties of human intervertebral disc tissue fragments in vitro

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